MOLECULAR MECHANICS CALCULATIONS OF PROTEINS - COMPARISON OF DIFFERENT ENERGY MINIMIZATION STRATEGIES

A general strategy for performing energy minimization of proteins usin g the SYBYL molecular modelling program has been developed. The influe nce of several variables including energy minimization procedure, solv ation, dielectric function and dielectric constant have been investiga ted in order to develop a general method, which is capable of producin g high quality protein structures. Avian pancreatic polypeptide (APP) and bovine pancreatic phospholipase A2 (BP PLA2) were selected for the calculations, because high quality X-ray structures exist and because all classes of secondary structure are represented in the structures. The energy minimized structures were evaluated relative to the corres ponding X-ray structures. The overall similarity was checked by calcul ating KMS distances for all atom positions. Backbone conformation was checked by Ramachandran plots and secondary structure elements evaluat ed by the length on hydrogen bonds. The dimensions of active site in B P PLA2 is very dependent on electrostatic interactions, due to the pre sence of the positively charged calcium ion. Thus, the distances betwe en calcium and the calcium-coordinating groups were used as a quality index for this protein. Energy minimized structures of the trimeric PL A2 from Indian cobra (N.n.n. PLA2) were used for assessing the impact of protein-protein interactions. Based on the above mentioned criteria , it could be concluded that using the following conditions: Dielectri c constant epsilon = 4 or 20; a distance dependent dielectric function and stepwise energy minimization, it is possible to reproduce X-ray s tructures very accurately without including explicit solvent molecules .