DR Ravi Profile
DR Ravi Profile
DR Ravi Profile
P RO F I L E
Dr. Ravi Muppirala has made Seminal contributions in Biophysics using NMR as a tool to study
structure and Dynamics of DNA & Proteins. He held academic positions at Carnegie-Mellon,
Syracuse and University of Michigan. His work is highly cited. He has been honored with national &
International awards. Recently, Dr. Ravi has contributed significantly to type-2 Diabetes Therapy and
delivered Keynote addresses at international Diabetes conferences. He has been invited to be on the
organizing Committees in T2D. He is on the Editorial Board of Archives of Metabolic Syndrome. He
has filed several patents in type-2 Diabetes and in voice-based biometrics. He has initiated founding an
international biomedical & high-performance computing research institute in Dubai.
Currently, Dr. Ravi is the CEO of MD Enterprises Global delivering patented technologies with
Biometrics for smart-governments & corporations. The AI baed product delivers highly-secure, user-
friendly, privacy-protected Government-to-Citizen services, extendable to corporations. He is also the
CEO of Global Gurus Conglomerate, specializing in executive management of Global (USA, Brazil,
India, UAE) IT infrastructure & development. His technology has been issued three patents in USA.
Dr. Ravi has been the Vice President & CTO for A3i, that offered “Software-as-a-Service” &
“Infrastructure-as-a Service” in Supply-chain & Logistics sector. He has architected state-of-the-art
Infrastructure (at Oracle’s Austin Data Center) to provide “cloud computing” as well as “e-commerce”
solutions. He has evolved many web-based customer-facing integration tools. He lives and breaths
ITIL, an essential set of guidelines to streamline IT processes and to provide optimal Service Delivery.
He is also an expert in implementing security and other best practices to ensure compliance to
regulations such as SOX. He has broad as well as in-depth exposure to all aspects of Data Center
Operations at GM North America Data Center (GMNA). He was also nominated for the GMNA
Security Lead position and was deputed as an SME to resolve Service Delivery issues successfully. He
has been overseeing every aspect IT management such as --- Researching technologies; Evaluating/
recommending Software & Hardware architecture that suits the current and future directions of the
business; Evolving KPIs & MDM Strategy for the organization; Overseeing software development for
ERPs, Mobile devices, with broad interpretation of SDLC; Managing vendors and the performing
suppliers.
Dr. Ravi is very accomplished in Data Analytics. Throughout his engineering, scientific and research
career he has implemented numerous analytical & statistical data models spanning statistical
correlations, numerical analysis and AI methods. He, in collaboration with the AI team from Syracuse,
has submitted NIH grants to ‘assign’ NMR data of proteins using a unique combination of Genetic
Algorithms and Neural Nets. He has written a seminal paper on correlated random motions in bio-
molecules like proteins, which can be applied to quantification methods in stock market analysis.
Dr. Ravi received NSTS award. His Ph.D. thesis won Geeta Udgoankar best thesis award in TIFR.
Dr. Ravi’s accomplishments are multi-faceted. Dr. Ravi has been offered US Residency - as an ‘Alien
of Extraordinary Ability’ (aka ‘genius visa’) under the initiative by President G.H.W. Bush.
EDUCATION
CERTIFICATIONS
ACADEMIC HONORS
• “Keck Scholar" at W.M. Keck Center for Advanced Training in Computational Biology, Pittsburgh
for the years 1992-94.
• “Bruker NMR Award for Young Scientists" for outstanding work in the field of NMR and its
applications for the year 1987.
• “Geeta Udgaonkar Award", awarded by TIFR for the outstanding thesis among the thirteen theses
submitted in 1987-88.
• “National Science Talent Search Scholarship", awarded by the Government of India in 1975.
Hardware: SUN Enterprise (3K & 5K), SunFire 280s, 440s, 880s, SUN netras, SUN T2000; IBM SP2 nodes, IBM RS
6000; HP-9000; DELL multi-processor servers; IBM-1170, Cyber-170; VAX-11/780, VAX-8600; SGIs; DECstations,
DEC-alphas; Sun Cluster, HBA, EMC Celera, Symmetrix.
Software: LINUX, APACHE, AIX 5L, SOLARIS 8 & 10, NAS & SAN, CA-Unicenter, WebLogic, Savvion, Siebel,
VMware, Sun Cluster, Sun-One, Tivoli, Patrol, HP OVO, VERITAS, Remedy ARS, OpenView ServiceDesk,
AlarmPoint, ARKEIA, IRIX, KSH, BASH, PERL, XEMACS, CVS, BugZilla, C/C++, Pascal, VMS, Fortran 90, HTML,
JavaScript, MySQL, Java, PHP, ITIL & SOX.
Training: VERITAS File-System & Volume Management, Vectorization & Parallelization, SAP NetWeaver 2004s,
Solaris-10, ITIL.
Languages: English, Portuguese (Brazil), Telugu, Hindi.
• Overseeing, at an executive level, IT infrastructure & development projects in India & Brazil.
Projects involved Tablet based technologies in Entertainment/Hospitality Sector; Complete IT
solutions (Software & hardware) for Institute of Engineers; Various IT projects in Supply Chain
Data & AI solutions.
• Managing all the IT & Operational components, as the CTO, in the virtual integration of Supply
Chain Logistics Software.
• Architected the infrastructure for supporting Oracle Transportation Management to support the
needs of extremely large customers with very robust integration to customer ERPs.
• Architected and offered a VPN (Virtual Private Net) based cloud computing solutions (SaaS &
IaaS) to large customers demanding high security of their data.
• Designed sophisticated integration architecture to ensure rapid customer deployment.
• Ensured that the service delivery from the Oracle Austin Data center is meeting the needs of the
customers in a timely manner.
• Implemented ITIL & SOX compliant policies and procedures to sustain stable production for all
customers and procured necessary compliance (e.g. SAS-70) from performing suppliers.
• Negotiated service delivery contracts for external integration with different customers and
suppliers.
• Evaluated different contractors and hired them to meet the needs of different customer launch
projects.
• Managed many projects for integrating mobile devices.
• Functioned as the Program Manager for Hyatt Corporation to implement PCI (Personal Card
Industry) DSS (Data Security Standard) compliance.
• Lead the Infrastructure Management component for GME SWB (General Motors Europe Sales
Work Bench) Project in all aspects and all the phages from development to production.
• Engineered Enterprise IT solutions for General Motors using UNIX, SAN, NAS technologies.
• Architected Enterprise level Hosting Services for General Motors (eg. OnStar) using SunOne,
Bea WebLogic, Sun Solaris 10 Clusters.
• Engineered migration of EPS application, involving set-up of new Solaris-9 servers, migration to
Oracle 9.2.0.8 and automatic TLSFTP setup and associated configuration & scripts.
• Consulted on the VCAMS projects involving WebLogic 8.1 & Savvion.
• Engineered all aspects of a two-node Sun Cluster 3.1u4 on Solaris-10 servers for GMAC backup
solution using Networker.
• Resolved issues that affect the SLA for various production processes that process logs at Yahoo.
• Resolved issues dealing with ETL (Extract, Transform and Load) & MDM (Master Data
Management) components of collected daily-data from point & click events.
• Ensured SLA compliance by monitoring FreeBSD servers, proprietary in-house built clusters,
NetApps Filers (NAS), NFS performance & NAGIOS alerts.
• Improved global service delivery and SLA compliance while serving as the SME (subject matter
expert) on deputation to EDWS SLA (GSC33 of General Motors). Functioned as the incident life
cycle manager and reduced process inefficiencies, through negotiations with the performing
suppliers, through process streamlining and through overall oversight and management.
• Managed deliverables within team for projects, tasks while supporting day-to-day activities to
maintain 95.05% uptime for both production and pre-production environments.
• Implemented & maintained GMNADC (GM North America Data Center) infrastructure and
services with complex technical specifications across their lifecycle.
• Evolved procedures and best-practices in order to maintain the GMNADC (GM North America
Data Center) systems and services to be stable, available, efficient and effective.
• Key projects are: Symmetrix Migration, Application Assurance Center Refresh Project, 64-node
Redhat Enterprise Linux Render Farm cluster Architecture Validation & Production Enrollment,
Manay virtualization projects (including VMware), Security Auditing, Validation of GM Sever
Standards (5.5 & 6.0 for Solaris 8 & 10; Sun Cluster 3.2) and releasing Gold Builds, Solaris 10
Containers for License Quorum, Stream-lining the Test-Lab Server environment.
• Provided direction for resolving technical incidents, problem management and root cause analysis.
• Provided summary of accomplishments, issues and work planned.
• Interacted with Infrastructure Operations Manager to address any specific resource issues.
• Suggested and implemented process improvements.
• Responded to off-hour incidents as needed & took ownership to coordinate resolution as quickly
as possible.
• Functioned as Senior Consultant/Architect for Production & Test-ring components of the GMNA
Data Center for General Motors at Warren.
• Work involves enrolling and maintaining servers and architecture validation and providing a pre-
production test-environment.
• Managed the Enterprise Directory Service for GM Pre-Production Environment. Initiated,
architected and tested the transition from NIS to LDAP. Contributed to many aspects of the
single-sign-on set-up.
• Won the e-award for resolving the UDP issue for General Motors that affected production
processes.
• Functioned as a System administrator and as a System architect for the SONY e-commerce set-up
in its development, UAT, QA & Production environments, comprising of SUN-enterprise servers,
fire-walls, load balancers running BEA WebLogic, Enfinity & IBM WebSphere e-commerce
applications.
• Wrote many shell scripts to automate their e-commerce needs.
• Directed the IT activities of the departmental Unit in order to support its educational and research
activities
• Maintained a number of Multiprocessor DELL Servers running RedHat Linux, after deploying
based on the architecture considering the requirements of the departmental units.
• Designed, steered and managed the complete design and deployment of the website with dynamic
updating using MySQL & PHP, on an APACHE web server.
• Performed System Administration & Network Security for an environment consisting of – Six
IBM RS6000 SP2 nodes; Twenty IBM RS6000 Servers; Two SUN Enterprise 3000; AIX 4.x;
Solaris 2.x; large-scale Oracle databases to maintain finance & HR of the University of Michigan.
• Deployed an IBM-LTO/Arkeia Back-Up System after speccing the requirements of the
departmental unit.
• Planned and installed appropriate file-systems etc. to manage & implement VERITAS volume
management using Raid-0 & Raid-5 on 120 GB SPARC Storage Array.
• Worked with an IBM team in planning and configuring SUN Enterprise 3000 systems to use
them, on a separate subnet, as load generators for performance evaluation IBM SP2 nodes that
ran a customized PeopleSoft package for the General Ledger of the University of Michigan.
• Completed an AIX 3.2.5 to AIX 4.2.1 upgrading project for twenty RS6000 production
workstations & worked with issues of dependencies and licensing of software packages.
• Used & Configured CA-Unicenter, BMC Patrol, Tivoli and other IBM products for configuring,
scheduling and monitoring various system administrative aspects.
• Worked with Software Configuration Management tools such as CVS, Clearcase & BugZilla.
• Participated in the implementation of the RFCs for RADB project (a public registry of routing
information for networks in the Internet); Wrote PERL scripts to query the database and send
automated billing invoices to participating ISPs;
• Monitored and resolved customer problems regarding all aspects of the maintainer objects in the
RADB.
• Coordinated the planning & commissioning of SUN Enterprise 3000 systems serving as large
scale database dealing with telecommunication.
• Wrote shell-scripts to streamline and ease system administrative tasks and to monitor security.
• Studied the need, efficacy & other security related issues in deploying “firewalls” for the
Administrative Services Computing Environment.
• Set-up and secured the departmental IT infrastructure with Kerberos, firewalls and TCP/IP
wrappers.
• Submitted several reports and an “Action Plan” for planning and implementing the “firewalls”.
• Monitored, continuously (during my work schedule), all the network components of LAN/WANs
(CICnet, MICHnet & Umnet) for performance, state, alarm conditions using Rover, Spectrum
and other unix/networking tools.
• Wrote up “Remedy Tickets” for all associated trouble reports to include updates, tracking and
closure.
• Worked with vendor/customer & telecom technicians in the troubleshooting of network problems.
• Corrected hardware and/or software components of LANs/WANs to arrive at final resolution of
outstanding network problems in a satisfactory manner to all parties.
• Acted as a liaison among all parties (viz. customer, vendor & staff) in the dissemination of
information concerning network problems.
• Developed and tested Fortran code to use Artificial Intelligence methods like Neural Networks
and Genetic Algorithms to automatically assign the two-dimensional NMR spectra of proteins.
• Administered a set of multi-platform-multi-OS UNIX workstations consisting of – a DECstation
5000(Ultrix), 3 SGI Indigo (IRIX), 7 Sun/SPARC workstations (SunOS 4.x, Solaris 2.x);
• Obtained a computational grant of 20 Units on CRAY C90 for studying: Relaxation and
Dynamics of Coupled Spins Systems Subjected to Pulsed or Continuous Radiofrequency fields
• Conceived, wrote & tested a Fortran Program (400KB Source), SPIDER, that performs complete
Quantum Mechanical Density Matrix calculations for simulating Spin Dynamics and runs on
CRAY C-90, Alliant Fx-8 and VAX systems.
• Wrote a Fortran program, MIDGE (150KB source), that uses experimental Overhauser effects to
obtain structural and dynamical information on proteins and nucleic acids and runs on CRAY
C-90 and VAX systems.
• Conceived, wrote & tested several Fortran Programs to determine the three dimensional structure
of DNA & Proteins and to simulate complex NMR spectra.
• Wrote programs to convert experimental data from Aspect-3000 (a Real-time computer) format to
a Mainframe (Cyber-170).
• Taught the assembly-language programming and the OS of Aspect-3000, a real-time computer
that interfaces NMR instruments.
• Served on the advisory committee for the computational support at the Institute (TIFR).
• Developed a new, elegant proof of Jennrich’s algorithm for “Multiple Linear Regression”. Coded
it in Fortran and implemented it on IBM-1170.
PROFESSIONAL EXPERIENCE:
• Assistant Research Scientist . . . . . . . . . . . . . . . 1995-Present.
The University of Michigan, Ann Arbor, MI.
• Senior Research Associate . . . . . . . . . . . . . . . . . . 1993-1994.
Syracuse University, Syracuse, NY.
• Research Associate . . . . . . . . . . . . . . . . . . . . . . 1991-1993.
Carnegie Mellon University, Pittsburgh, PA.
• Post-Doctoral Research Associate . . . . . . . . . . . . . . 1988-1991.
Carnegie Mellon University, Pittsburgh, PA.
EDUCATION:
• Doctor of Philosophy in Chemistry . . . . . . . . . . . . . . March 1988.
Tata Institute of Fundamental Research (TIFR), Bombay, India.
Ph.D. Thesis: Two Dimensional NMR Techniques and their Applications to Solution
Structure of Nucleic Acids.
• Master of Science(Hons.) in Chemistry . . . . . . . . . . . . June 1982.
Birla Institute of Technology and Science (BITS), Pilani, India.
Master’s Thesis: Multiple Linear Regression
• Bachelor of Engineering(Hons.) in Chemical Engineering . . . . June 1982.
Birla Institute of Technology and Science (BITS), Pilani, India.
Practice School II Projects: Study of CS2 Losses in CS2 Plant & A Feasibility Study
on Waste Heat Recovery from Calcinator Flue Gasses at Indian Rayon Corporation,
Veraval, India.
ACADEMIC HONORS:
• “Keck Scholar” at W.M. Keck Center for Advanced Training in Computational Biol-
ogy, Pittsburgh for the years 1992-94.
• “Bruker NMR Award for Young Scientists” for outstanding work in the field of NMR
and its applications for the year 1987.
• “Geeta Udgaonkar Award”, awarded by TIFR for the outstanding thesis among the
thirteen theses submitted in 1987-88.
• “National Science Talent Search Scholarship”, awarded by the Government of India
in 1975.
1
GRANTS:
• Relaxation and Dynamics of Coupled Spins Systems Subjected to Pulsed or Con-
tinuous Radiofrequency Fields: 20 Units on C90 at the Pittsburgh Supercomputing
Center.
• Algorithms for Assigning NMR Spectra of Biomolecules: Under revision after unsuc-
cessful submissions to NSF & NIH.
• Mechanisms of Thermostabilization of tRNA by Base Modification: Submitted to
NSF (With total costs $ 397,295 for October 2000 - September 2003).
PUBLICATIONS:
• 21 Publications in refereed Journals
• 18 Presentations in Conferences
• 140 Citations in Journals and Books
RELEVANT STUDIES:
Structure and Dynamics of Proteins and Nucleic Acids; Multidimensional homonu-
clear and heteronuclear NMR; NMR Instrumentation; Handling Biological Molecules; Spin-
Dynamics Theory and Simulations; Application of AI (Neural Nets and Genetic Algo-
rithms) to NMR.
2
Teaching Approach, Experience & Interests
Approach:
I believe that the best way to teach is to emphasize the counterpoint between intuition
and technical rigor. Generally, students have considerable difficulty understanding the
connection between the two. They can understand intuitive ideas and they can follow
logical arguments, but they often find it hard to pass back and forth between these modes
of thinking.
Many truths of science that seem obvious to students with good intuition nevertheless
have rigorous treatments that are daunting when written out in full detail. In such cases, I
like to elicit feedback from students as to why the propositions seems obvious (or, at least,
plausible). Sometimes students give excellent reasons why a proposition is true and it is
possible to convince them that a seemingly intimidating formal argument is nothing more
than a precise, fleshed out version of their intuitive understanding.
The converse situation also occurs frequently. Sometimes a proposition has a treat-
ment that is logically straightforward, but that is not very intuitively satisfying. In our
own research we constantly notice the di↵erence between a rigorous treatment that merely
proves and a treatment that really explains. Students, I think, are more sensitive to this
point than professional scientists. Scientists always prefer that a proof or a solution to a
problem should have an interesting intuition underlying it, but, nevertheless, we accept
purely formal arguments as fully adequate. Many students do not feel comfortable with
a formal argument even a very simple one unless it is possible to identify some key ideas
that explain why the logic flows the way it does. Also, constantly emphasizing ideas and
intuitions helps to reduce the students’ sense of the “distance” between themselves and
their teacher.
I also strive to build up the concepts that are being taught, when ever possible, by
conducting the class by seeking what di↵erent students think of it. Then, I point out why
the wrong answers/approaches are not appropriate by suitable reasoning and examples.
Then, I take o↵ from the correct answers/approaches. Of course, such participation by
students is facilitated by indicating certain credit (say, 5%) for class participation.
One of the key elements that I have learnt over years of learning and research is that
we feel difficulty in understanding certain concepts primarily due to gaps or holes in all
the concepts that are prerequisites. Students, often have the same problem and di↵erent
students have di↵erent holes, with varying diameters. So, in order to help them, I attempt
to find these holes with patient questioning. These holes can be filled by either answering
them or by directing them to correct resources. I find that such an approach, albeit time
consuming, helps many students who are willing to put the requisite e↵ort.
When I design a test/exam, I generally try to divide it into three parts. The first part
deals with the minimal information and knowledge the course is aimed at. The second part
deals with in depth testing of concepts. The third part gives attempts to challenge the
advanced students with the thoroughness of concepts and knowledge and provides scope
to exhibit their creativity.
3
Experience:
I strongly believe that teaching at any level (graduate and undergraduate) and success-
ful research mutually reinforce each other. Therefore, I have always been very interested
in any opportunities to teach. While I was working for my masters I was able to teach
under the “Earn While You Learn Program” of BITS. In my graduate work at TIFR, I
had opportunity to teach graduate students and also to teach at a workshop on NMR.
At Carnegie Mellon University, I have taught Organic Chemistry-I at the under-
graduate level as a full-fledged instructor. I have also substituted, several times, Prof.
George Levy for his General Chemistry courses at Syracuse University during his planned
absences.
Interests:
Listed below are some of the courses that I would be interested in teaching.
• NMR Spectroscopy
• General Chemistry
• Physical Chemistry (both at Graduate and Undergraduate levels)
• Organic Chemistry (at Undergraduate level only)
• Elementary Quantum Chemistry
• Analytical Chemistry
• Biophysical Chemistry/Molecular Biophysics
• Biochemistry
• Introduction to Molecular Biology
• Undergraduate Physics
• Quantum Mechanics (both at Graduate and Undergraduate levels)
• Thermodynamics (Chemical/Chemical Engineering)
• Heat and Momentum Transfer
• Physics of Materials
• Structural and Chemical Characterization of Materials
4
JOURNAL PUBLICATIONS:
5
M.Ravikumar
Chem. Phys. Lett., 144, 521 (1988).
(J13) Relaxation and Dynamics of Coupled Spin Systems Subjected to Continuous Radiofre-
quency Fields.
M.Ravikumar, R.Shukla and A.A.Bothner-By
J. Chem. Phys., 95, 3092 (1991).
(J14) A Two-Dimensional NMR Experiment for the Correlation of Spin-Locked and Free
Precession Frequencies.
M.Ravikumar and A.A.Bothner-By
J. Amer. Chem. Soc., 115, 7537 (1993).
(J15) Exact Evaluation of the Line-Narrowing E↵ect of the Lee-Goldburg Pulse Sequence
in Solid-State NMR Spectroscopy.
M.Ravikumar and A.Ramamoorthy
Chem. Phys. Lett., 286, 199 (1998).
(J16) Incorporation of Temporally Correlated Internal Motions into the Magnetic Reso-
nance Relaxation Treatment while Considering Interference of Di↵erent Relaxation
Mechanisms.
M.Ravikumar
Chem. Phys. Lett., 319, 197 (2000).
6
UNDER PREPARATION, SUBMITTED:
(U1) Observable Operator Formalism and its application to the Dynamics of A Two Spin
System.
M.Ravikumar
Under Preparation
(U2) Role of Population Distributions in Multiple Quantum Transitions.
M.Ravikumar
Under Preparation
(U3 A Method for designing Time-Domain Radio-Frequency Pulse Shapes to Achieve
Frequency-Selective Excitation, while Accounting for Scalar Coupling.
M.Ravikumar
Under Preparation
(U4) Sequential Assignment of Nuclear Magnetic Resonance Spectra of Proteins Based on
Genetic Algorithms.
M.Ravikumar, C.K.Mohan, K.G.Mehrotra and G.C.Levy
Under Preparation
(U5) Studies of Local Mobility in Ferricrocine by Relaxation Matrix Approach, Combining
NOESY and CAMELSPIN data.
M.Ravikumar, M.Pons, J.Jimenez-Barbero and M.Llinas
Under Preparation
CONFERENCE PRESENTATIONS:
7
National Conference on Spectroscopy and Theoretical Chemistry,
Calcutta, India. (Dec.5-7, 1985)
(C6) A New scaling scheme for Two Dimensional Homonuclear Correlated Spectroscopy.
R.V.Hosur, M.Ravikumar and A.Sheth
Proceedings of XXIII congress ampere on Magnetic Resonance, ROMA 1986
pp 572.
(C7) Scaling in Two Dimensional Correlated Spectroscopy.
R.V.Hosur, M.Ravikumar and A.Sheth
XII International Conference on Magnetic Resonance in Biological
Systems, Todtmoos, West Germany. (8 - 12 September, 1986)
(C8) Solution Structure of d-CTCGAGCTCGAG using 2D NMR: Role of DNA Structure
in Recognition.
A.Sheth, M.Ravikumar, R.V.Hosur, G.Govil and H.T.Miles
XII International Conference on Magnetic Resonance in Biological
Systems, Todtmoos, West Germany. (8 - 12 September, 1986)
(C9) Strategies to Obtain 2D Structural Information of Nuclear Acids: An Application to
d-(GAATTCCCGAATTC).
M.Ravikumar, A.Sheth, R.V.Hosur, G.Govil and H.T.Miles
XII International Conference on Magnetic Resonance in Biological
Systems, Todtmoos, West Germany. (8 - 12 September, 1986)
(C10) Origin of Primitive Cells II: A Physico-chemical Pathway to the Evolution of Primitive
Genetic Apparatus.
M.Ravikumar and G.Nareshkumar
ISSOL 86, Berkeley, USA. (21 - 25 July, 1986)
(C11) Origin of Primitive Cells I: Biochemical Evolution Within Bilayer Lipid Vesicles.
G.Nareshkumar and M.Ravikumar
ISSOL 86, Berkeley, USA. (21 - 25 July, 1986)
(C12) Distance Contours to Interpret NOESY Spectra of Nucleic Acids.
M.Ravikumar and R.Ajaykumar
XIII International Conference on Magnetic Resonance in Biological
Systems, Madison, USA. (14 - 19 August, 1988)
(C13) Observable Operator Formalism.
M.Ravikumar
High Resolution NMR in Solids, Boston, USA. (19 - 21 January, 1989)
(C14) New Experiments in the Rotating Frame.
M.Ravikumar and A.A.Bothner-By
XIV International Conference on Magnetic Resonance in Biological
Systems, Warwick, UK. (9 - 14 September, 1990)
(C15) More Experiments in the Rotating Frame.
A.A.Bothner-By, M.Ravikumar and D.Bennet
31st Experimental Nuclear Magnetic Resonance Spectroscopy Conference,
Pacific Grove, CA, USA. (1 - 5 April, 1990)
(C16) Dynamics of Spins Under Spin-Locked Conditions.
M.Ravikumar, R.Shukla and A.A.Bothner-By
8
31st Experimental Nuclear Magnetic Resonance Spectroscopy Conference,
Asilomer, Pacific Grove, CA, USA. (1 - 5 April, 1990)
(C17) Estimation of Number of Peaks in NMR Spectra.
M.Ravikumar, A.Diop, P.N.Borer, G.C.Levy
35th Experimental Nuclear Magnetic Resonance Conference, Asilomer,
Pacific Grove, CA, USA. (10 - 15 April, 1994)
(C18) Capturing Biomolecular Correlated Internal Motions via NMR Cross-correlation.
M.Ravikumar and P.Kumar
XII International Conference on Magnetic Resonance in Biological
Systems, Toronto, Canada. (25 - 30 August, 2002)
9
The following have cited one or more publications of Muppirala Ravikumar
BOOKS:
1 NMR of Proteins and Nucleic Acids
Kurt Wuthrich
John Wiley (1986), pp 61, 236
2 Two Dimensional NMR Spectroscopy
Jan Schraml and Jon M. Bellama
John Wiley (1988), pp 105
3 Recent Developments in Multipulse NMR
David L. Turner
"Annual Reports on NMR Spectroscopy, Vol. 21"
Academic Press (1989), pp 179, 180
JOURNALS:
1 Journal of Magnetic Resonance, 63, 107-114 (1985)
2 FEBS Letters, 191, 92-96 (1985)
3 Journal of Magnetic Resonance, 65, 375-381 (1985)
4 Journal of Molecular Biology, 190, 439-453 (1986)
5 Journal of Magnetic Resonance, 69, 418-425 (1986)
6 Journal of Magnetic Resonance, 70, 213-218 (1986)
7 Journal of Magnetic Resonance, 70, 169-172 (1986)
8 Current Science, 55, 597-605 (1986)
9 FEBS Letters, 205, 71-76 (1986)
10 Biochemical and Biophysical Research Communications, 139, 1224-1232
(1986)
11 European Journal of Biochemistry, 158, 323-332 (1986)
12 Journal of Natural Products-Lloydia, 49, 787-793 (1986)
13 Bioorganicheskaya Khimiya, 13, 1194-1204 (1987)
14 Journal of Magnetic Resonance, 71, 539-543 (1987)
15 Journal of Magnetic Resonance, 74, 352-355 (1987)
16 Current Science, 56, 166-167 (1987)
17 Journal of Organic Chemistry, 52, 5136-5143 (1987)
18 Journal of Magnetic Resonance, 73, 417-422 (1987)
19 Journal of Biomolecular Structure & Dynamics, 4, 621-649 (1987)
20 European Journal of Biochemistry, 166, 87-101 (1987)
21 Chemical Physics Letters, 138, 431-435 (1987)
22 Chemical Physics Letters, 140, 565-566 (1987)
23 Biopolymers, 26, 1301-1313 (1987)
24 Biochemistry, 26, 1315-1322 (1987)
25 Biochemistry, 26, 3734-3744 (1987)
26 Biochemical and Biophysical Research Communications, 144, 26-34 (1987)
27 Molecular Biology, 21, 493-512 (1987)
10
28 Magnetic Resonance in Chemistry, 26, 927-944 (1988)
29 European Journal of Biochemistry, 178, 1-38 (1988)
30 Angewandte Chemie, 27, 490-536 (1988)
31 Analytical Chemistry, 60, R1-R28 (1988)
32 Nucleic Acids Research, 16, 5713-5726 (1988)
33 Journal of Molecular Biology, 202, 139-155 (1988)
34 Journal of Magnetic Resonance, 76, 218-223 (1988)
35 Journal of Biosciences, 13, 71-86 (1988)
36 Journal of Biomolecular Structure & Dynamics, 6, 421-441 (1988)
37 Journal of the American Chemical Society, 110, 1598-1602 (1988)
38 International Journal of Biochemistry, 20, 721-730 (1988)
39 Inorganica Chimica Acta, 140, 373-374 (1987)
40 FEBS Letters, 233, 319-325 (1988)
41 Chemical Physics Letters, 144, 521-522 (1988)
42 Biochemistry, 27, 3858-3867 (1988)
43 Biochemistry, 27, 6013-6020 (1988)
44 Uspekhi Fizicheskikh Nauk, 156, 653-682 (1988)
45 Journal of Biochemical and Biophysical Methods, 17, 253-276 (1988)
46 Journal of Biomolecular Structure & Dynamics, 7, 557-589 (1989)
47 Uspekhi Khimii, 58, 1318-1353 (1989)
48 Journal of the American Chemical Society, 111, 5482-5483 (1989)
49 Magnetic Resonance in Medicine, 11, 288-294 (1989)
50 Journal of Molecular Structure, 194, 33-43 (1989)
51 Biochemistry, 28, 1462-1471 (1989)
52 Biochemistry, 28, 5240-5249 (1989)
53 Biochemistry, 28, 7275-7282 (1989)
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SUMMARY OF RESEARCH WORK:
14
complete theoretical analysis has been developed to delineate the role of population dis-
tribution in creating non-zero MQ coherences by a single non-selective pulse. [References
to Publications: J5, J12]
(5) Dynamics of Spins under Spin-Locked Conditions:
A Spin Dynamics simulation program, SPIDER (SPIn Dynamics incorporating com-
pletE Relaxation), for the prediction of spin trajectories in systems of two or more spins
evolving under the influence of the static field, an applied radio frequency field, chemical
shifts, spin-spin couplings and magnetic dipolar relaxation has been developed. It has
been shown that it is necessary to retain the non-secular elements of the relaxation matrix
in order to obtain correct results and as a result two unexpected features are predicted:
frequency and phase shifts in spectra of two non-spin-coupled nuclei with relaxation rate
comparable to frequency separation and unusually intense magnetizations in the locked
state of two spins with the radio frequency applied at the centre of the spectrum. This
computational approach has been developed with chiefly two goals in mind — (1) To
enable deeper understanding of complex pulse sequences which especially involve long
radio-frequency pulses as well as to simultaneously understand the e↵ect of relaxation on
such pulse sequences. (2) To enable simulation of multidimensional NMR spectra involv-
ing Overhauser e↵ects (eg. NOESY, 2D-CAMELSPIN) of large bio-molecules so as to
determine their three-dimensional structure more accurately. [References to Publications:
J13]
(6) New Experiments in the Rotating Frame:
Based on the SPIDER simulations, an interesting form of 2-D spectroscopy has been
developed, using the sequence: DELAY-SPINLOCK(t1 )-FID(t2 ). This is the first experiment
which allows direct observation and monitoring of the Hartman-Hahn transitions. The de-
lay allows relaxation to the thermalPequilibrium state.
P Evolution during
Pn t1 is governed by
n
the spin-lock Hamiltonian, HSL = k=1 !k Ikz + k<l Akl Ik Il + k=1 !r.f. (cos Ikx +
sin Iky ) and typically involves rapidly decaying (r.f. field inhomogeneity) precessions
about the e↵ective fields, more slowly decaying Hartman-Hahn type transitions and even-
tual production of steady-state locked state. The 2-D spectrum shows the connections
between the elements of the spin-locked and free-precession Hamiltonians and yields infor-
mation on transverse NOEs. Variations on the basic experiment, named LOUSY (LOck
Unprepared Spins spectroscopY), are being investigated to achieve separation of Hartman-
Hahn e↵ects from CAMELSPIN e↵ects and to extract relaxation parameters. [References
to Publications: J14]
(7) Structure and Dynamics of Bio-Molecules from the Simultaneous
Use Of NOESY and CAMELSPIN Experiments:
A Fortran program, MIDGE, has been developed in order to obtain the local mobility
e↵ects along with the structure of proteins and nucleic acids. Experimentally measured
Overhauser matrix is used to obtain longitudinal and transverse cross-relaxation rates. The
ratio these cross-relaxation rates is used to obtain “local” correlation times and distances.
This method has been successfully used to obtain the structure-dynamics of Ferricrocine.
[References to Publications: U5]
15
(8) Structural Studies on Plasminogen Kringle 4:
Plasminogen (PGN) is a multi-domain protein that plays a central role in fibrinolysis
and in overall hemostasis. PGN Kringle 4 (K4), one of the domains of PGN, contains a
binding site for L-lysine and has been proposed to be mediating interactions with lysyl
side chains exposed within fibrin clots. This part of my research focuses on the solution
structure determination of human PGN K4 both in the absence and presence of ligands
(i.e. 6-aminohexanoinc acid, p-benzylamine sulfonic acid etc.) Most of the two-dimensional
NMR data that is required has been acquired and the assignment of proton resonances is
underway. [References to Publications: B4]
(9) Domain-Domain Interactions and Regions of Reversible Unfolding
of the Multidomain Protein BM 06.022:
BM 06.022 is a multidomain protein containing the kringle 2 (K2) and protease do-
mains of tPA (tissue-type Plasminogen activator) and was cloned at Boehringer Mannheim
GmBH. While the ultimate aim of this project is to obtain the 3D structure of this protein
as well as to understand its interaction with relevant ligands, the whole protein is too big
to be studied with present NMR technology. In the process of investigating appropriate
conditions to collect NMR data on this protein, a number of 1D spectra have been obtained
varying temperature and pH. These results seem to imply that BM 06.022 under acidic
conditions allows reversible thermal unfolding of K2 domain but not the the protease do-
main. The protease domain by itself also undergoes irreversible thermal unfolding in both
acidic and basic conditions. In BM 06.022 pH titration implies that both K2 and protease
domains undergo reversible unfolding in the acidic range, while only K2 is reversible in the
basic range. The pH titration of protease itself shows similar behaviour as in BM 06.022.
[References to Publications: B4]
(10) Fully Automated Methods for the Sequential Assignment of Multi-
Dimensional NMR Spectra of Proteins and Nucleic Acids:
Methods have been developed to accomplish the Sequence Specific assignment of NMR
spectra of Proteins and Nucleic Acids, using a strategic combination of specifically de-
signed Genetic Algorithms and Gradient Descent methods. The approach has been used
to successfully verify the complete sequence specific assignment of the spinach Acyl Carrier
Protein (77 Residues) and of the phospho carrier protein IIIGlu from E.coli.
These methods are currently being tested with the 3D heteronuclear data of a 172
residue DNAK binding protein. Currently, only HNCA (332 peaks) and HNCAHA (280
peaks) are being used with a minimal amount of “anchoring” information on side chains
from HCCH spectra. In this case the anchors used are ALA, GLY, THR, VAL. So far this
approach has identified about 96 residues correctly.
This is really encouraging since, none of the 3D experiment which filters through
the carbonyl (like HN(CO)CA) were used and that only limited number of side-chain
assignments to achieve progress. Of course, the program can utilize all the available data.
But the strength of this approach is that it can start working with a minimal amount of
experimental data (in this case HNCA and HNCAHA data) and can request specific side-
chain information that it requires in order to complete the assignment. This “incremental”
approach, in which one begins working with any reasonable combination of back-bone and
16
side-chain information and further refining it as and when more data becomes available is
efficient and flexible. [References to Publications: U4]
(11) Studies of Internal Dynamics of DNA with Helix Imperfections:
Local variations in the motion of an 18-mer DNA sequence,
d-GCGTCGCTTCGGCGTCGC, are being studied by using multi-dimensional 1 H and
13
C NMR spectroscopy. Initially, all non-exchangeable 1 H resonances are being assigned
by NOESY AND COSY spectra. Ambiguous and overlapping resonances will be resolved
by 1 H and 13 C correlation spectroscopies. experimental observations of various relaxation
parameters in conjunction with phenomenological motional models are being used to gain
insight into the variations of internal motion.
(12) Observable Operator Formalism:
A general Operator Formalism has been developed to obtain useful formulae helpful to
calculate exact spin-dynamics for strongly coupled spins. The formalism has been applied
to develop formulae for the dynamics of two spin system, where the two spins are chemically
shifted and are coupled by isotropic scalar coupling or truncated dipolar coupling. The
formalism gives the refocussing e↵ect of ⌧ 180 ⌧ pulse sequence for coupled spin systems.
This formalism is extendable to other bilinear interactions. [References to Publications:
U1]
(13) Physico-chemical Hypothesis to Explain the Origin of Primitive
Cells:
A pathway has been visualized to describe the origin of primitive cells starting from
a stage of biochemical evolution. The pathway is based on physicochemical principles and
the principle of continuity. The hypothesis is verifiable experimentally. [References to
Publications: B2, B3]
(14) Analysis of the Line-Narrowing Effect of the Lee-Goldburg Pulse
Sequence in Solid-State NMR Spectroscopy:
Magic-angle irradiation or Lee-Goldburg (LG) pulse sequence is being routinely used
in high resolution NMR spectra of solids to suppresses the homonuclear dipolar interaction
while simultaneously scaling the chemical shift and heteronuclear dipolar interactions. In
this communication, a general and detailed spin dynamics calculation procedure to evaluate
the performance of the LG sequence is presented which yields an expression for the dipolar
scaling factor for an arbitrary rf strength, rf o↵set and windowed observation. This analysis
is expected to be useful in designing new multiple-pulse sequences for scaling the dipolar
interaction. [References to Publications: J15]
(15) Extraction of Correlated or Concerted Internal Motions by Ex-
tending NMR Relaxation Treatment:
Correlated internal motions are incorporated into the magnetic resonance relaxation
treatment, while taking into account the interference e↵ects between two di↵erent mecha-
nisms of relaxation. The joint probability density function due to two di↵erent stochastic
processes, responsible for spin relaxation, is approximated in terms of the individual proba-
bility density functions. A parameter that is indicative of the degree of correlation between
17
the two stochastic processes is introduced in this treatment. Such a parameter of dynamics,
for the first time, provides a way of observing and analyzing correlated internal motions
in macromolecules. This is especially important in biomolecules such as proteins and nu-
cleic acids where the correlated internal motions play a significant role in their function.
Expressions for cross-correlation spectral densities are given for some common interfer-
ence mechanisms, so that the theory can be directly applied to appropriate experimental
measurements. [References to Publications: J16, C18]
18