This research is concerned with the problem of calculating protein structure.
The aim i s to determine how interatomic interactions lead to the native three- dimensional structure of a protein. The methods used are based on statistical mechanics, relying heavily on both theory and computer simulations (Monte Carlo and energy minimization). During the past year, we have continued the derivation of a new force field, as an improvement over our current one (ECEPP). As additional innovations in methodology, we parallelized some of our algorithms for use on the KSR1 computer, made a statistical analysis of side-chain conformations in proteins , developed a method to carry out normal mode analyses of large macromolecules , applied an entropy- sampling Monte Carlo method to identify the basic statistical mechanical features of the protein folding problem , analyzed the electrostatic contribution to the helix-coil transition of poly (L-lysine) in water and aqueous methanol solutions , solved the problem of the end-to-end distribution function for a finite polymer chain, developed methods to pack polypeptide chains and small molecules in arrays and in crystals, and developed a united-residue potential. In addition to the development of methodology, we applied our algorithms to two biological problems, viz., the structure of collagen and the conformation of angiotension II and the mechanism of the activation of its receptor. In as-yet-unpublished work, we have focused much of our effort to surmount the multiple- minima problem arising from the complexity of the energy landscape; most of the attention on this problem is being devoted to improving and implementing our diffusion equation method to smooth out the energy landscape to be able to identify the global minimum. In addition, work is being carried out to complete the development of our new force field and to incorporate hydration into it with the aid of ab initio quantum mechanical and crystal-packing calculations.
| Chiang, Chi-Tung; Shores, Kevin S; Freindorf, Marek et al. (2008) Size-restricted proton transfer within toluene-methanol cluster ions. J Phys Chem A 112:11559-65 |
| Kazmierkiewicz, Rajmund; Liwo, Adam; Scheraga, Harold A (2003) Addition of side chains to a known backbone with defined side-chain centroids. Biophys Chem 100:261-80 |
| Kazmierkiewicz, Rajmund; Liwo, Adam; Scheraga, Harold A (2002) Energy-based reconstruction of a protein backbone from its alpha-carbon trace by a Monte-Carlo method. J Comput Chem 23:715-23 |
| Liwo, Adam; Arlukowicz, Piotr; Czaplewski, Cezary et al. (2002) A method for optimizing potential-energy functions by a hierarchical design of the potential-energy landscape: application to the UNRES force field. Proc Natl Acad Sci U S A 99:1937-42 |
| Scheraga, Harold A; Pillardy, Jaroslaw; Liwo, Adam et al. (2002) Evolution of physics-based methodology for exploring the conformational energy landscape of proteins. J Comput Chem 23:28-34 |
| Scheraga, Harold A; Vila, Jorge A; Ripoll, Daniel R (2002) Helix-coil transitions re-visited. Biophys Chem 101-102:255-65 |
| Pillardy, J; Arnautova, Y A; Czaplewski, C et al. (2001) Conformation-family Monte Carlo: a new method for crystal structure prediction. Proc Natl Acad Sci U S A 98:12351-6 |
| Vila, J A; Ripoll, D R; Scheraga, H A (2001) Influence of lysine content and pH on the stability of alanine-based copolypeptides. Biopolymers 58:235-46 |
| Pillardy, J; Czaplewski, C; Liwo, A et al. (2001) Recent improvements in prediction of protein structure by global optimization of a potential energy function. Proc Natl Acad Sci U S A 98:2329-33 |
| Czaplewski, C; Rodziewicz-Motowidlo, S; Liwo, A et al. (2000) Molecular simulation study of cooperativity in hydrophobic association. Protein Sci 9:1235-45 |
Showing the most recent 10 out of 20 publications
