Physics-based prediction of structure and folding pathways of proteins

	Special Guest Lectures
	Physics-based prediction of structure and folding pathways of proteins
	Jozef Adam Liwo

	Life Sciences Building Annex A101 July 10, 2006 - 03:00 pm
Abstract: Prediction of protein structure from amino-acid sequence has become a major problem in the genome era because of growing discrepancy between the number of known sequences of biologically important proteins and the number of structures that can be solved experimentally. Structure prediction methods can be divided into knowledge-based methods which make explicit use of protein structural databases and physics-based methods in which a structure is predicted as a collection of structures with the lowest free energy at physiological temperature (the Anfinsen hypothesis). To date, the knowledge-based methods have been more successful but onlythe physics-based methods enable us to understand why is a particular structure picked out of zillions of possible structures and how is it formed (in other words, what are the possible folding pathways). In this talk I will describe the physics-based united-residue UNRES model and the corresponding force field which is being developed in our laboratory. Use of such reduced representation enables us to reduce the computational time by a factor of 4,000 compared to all-atom molecular dynamics simulations with explicit solvent, which enables in silico folding simulations of proteins in real time. The presented examples of application of UNRES will include performance of the force field in the Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction, CASP3-CASP6, simulations of folding pathways, and use of the results of simulations to derive kinetic equations of folding.

Speaker's Bio: Jozef Adam Liwo Born: April 15, 1960, Gdansk, Poland Citizenship: Polish ### Personal: Married since 2002, wife: Katarzyna Liwo; daughter, Joanna Alicja Liwo, born 8/8/2003. ### Languages: Polish (fluent), English (fluent), Russian (good), German (basic), French (basic), Spanish (basic), Latin (basic), Chinese (basic). ### Positions (present): 1. Full Professor since 2004, Faculty of Chemistry, University of Gdansk, Poland 2. Senior Research Associate at Cornell University since 2003 (working with Professor Harold A. Scheraga). ### Scientific degrees and titles: 1. MSc in Chemistry: 1983, University of Gdansk, Poland (supervisor: dr Jurand Czerminski, University of Gdansk) 2. Ph.D. in Chemistry: 1989, University of Gdansk, Poland (suprvisor: prof. Zbigniew Grzonka, University of Gdansk) 3. DSc. (habilitation) in Chemistry: 1997, University of Gdansk, Poland 4. Professor of Chemistry (this is a scientific title in Poland), 2001 ### Employment record: 1. University of Gdansk, Poland a. Teaching Assistant (Chemistry): 1983-1989 b. Assistant Professor (Chemistry): 1989-2001 c. Assistant Professor: 2001-2004 2. Cornell University (in Professor Harold A. Scheraga group) a. Postdoctoral associate: 1990-92 and 1994-95 b. Visiting Scientist: short (3-6 month visit): 1993, 1996-2003. c. Senior Research Associate: since December 1, 2003 3. Informatics Center, Technical University of Gdansk, Poland a. Deputy Director for Scientific Affairs, 2001-2003. ### Memberships and boards: 1. President, Scientific Council of Academic Metropolitan Network, Gdansk, Poland, 1998-2001. 2. Polish Society of Computer Simulations, since 2000 3. Scientific Society of Gdansk, since 2005. ### Present scientific interests: 1. Prediction of protein structure from amino-acid sequence using physics-based methodology and theoretical investigation of protein folding (main activity). 2. Prediction of protein-folding pathways using Langevin dynamics with a physics-based united-residue force field. 3. Conformational analysis of small peptides, such as enkefalin and neurohypophyseal-hormone analogs using Monte Carlo methods and empirical force fields and application of the results in structure-activity correlation. ### Past research interest: 1. Quantum-mechanical investigations of the mediation of superoxide generation by the anthracenedione-based anticancer drugs; 2. Quantum-mechanical investigations of the mechanisms of peptide-bond cleavage by cysteine proteases and design of inhibitors of this process, which can be implemented as anti-bacterial and anti-fungal drugs. 3. Application of QSAR to study biological activity of neurohypophyseal hormone analogues. Courses taught at present (University of Gdansk): 1. Lecture in Advanced Theoretical Chemistry (Statistical Thermodynamics and Molecular Simulations). 2. Molecular Modeling (lectures and lab classes). 3. Numerical Methods is Chemistry (for advanced students). 4. Data Analysis in Chemistry (for advanced students). 5. Parallel Programming with MPI (for advanced students). #### Courses taught in the past (University of Gdansk): 1. Elementary Chemistry (labs and calculus classes). 2. Computer Science in Chemistry (lectures and lab classes). 3. Inorganic Chemistry (labs and seminar classes). 4. Physical Chemistry (calculus classes). 5. Programming in FORTRAN (lectures and lab classes) #### Supervised graduate works: * 5 completed * 2 pending. ### Publications: 170 papers in English in international journals and refereed conference proceedings (148 papers in ISI journals), one paper in Polish (an invited review for Wiadomosci Chemiczne) and a co-author of book chapter.

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