Design of a Molecular Dynamics Model for High-Performance Computing of Conformational Changes in Microtubule Protofilaments Associated with the Anticancer Drug Taxol
Fedorov V.A.1,2, Kholina E.G.2, Bulatov M.F.3,2, Kovalenko I.B.2,3,4
1Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
2Lomonosov Moscow State University, Moscow, Russia
3Scientific and Technological Center of Unique Instrumentation of the Russian Academy of Sciences, Moscow, Russia
4Pskov State University, Pskov, Russia
Abstract. Molecular dynamics models of tubulin tetramers in complex with the anticancer drug taxol were created based on high-resolution spatial structures (PDB ID 3J6G). We tested performance of various computational architectures in molecular dynamics calculations of tubulin tetramers. We revealed the optimal computer architecture and carried out three 1 μs molecular dynamic trajectories of taxol-bound tubulin tetramer. We analyzed the conformational flexibility of tubulin tetramers in a complex with taxol, calculated the Euler angles for intra- and inter-dimer interfaces of the protofilament, as well as the degree and direction of protofilament bending. The stiffness of protofilaments was studied using the energy equipartition theorem. The results allowed us to conclude that taxol binding reduces stiffness at both the inter- and intra-dimer interfaces, which may facilitate the process of microtubule assembly.
Key words: molecular dynamics, microtubules, tubulin, taxol, Euler angles, performance of molecular-dynamics calculations.