Prediction of conformation of rat galanin in the presence and absence of water with the use of monte Carlo methods and the ECEPP/3 force field

Abstract

The conformation of the 29-residue rat galanin neuropeptide was studied using the Monte Carlo with energy minimization (MCM) and electrostatically driven Monte Carlo (EDMC) methods. According to a previously elaborated procedure, the polypeptide chain was first treated in a united-residue approximation, in order to enable extensive exploration of the conformational space to be carried out (with the use of MCM). Then the low-energy united-residue conformations were converted to the all-atom representations, and EDMC simulations were carried out for the all-atom polypeptide chains, using the ECEPP/3 force field with hydration included. In order to estimate the effect of environment on galanin conformation, the low-energy conformations obtained as a result of these simulations were taken as starting structures for further EDMC runs that did not include hydration. The lowest-energy conformation obtained in aqueous solution calculations had a nonhelical N-terminal part packed against the nonpolar face of a residual helix that extended from Pro13 toward the C-terminus. One next lowest-energy structure was a nearly-all-helical conformation, but with a markedly higher energy. In contrast, all of the low-energy conformations in the absence of water were all-helical differing only by the extent to which the helix was kinked around Pro13. These results are in qualitative agreement with the available NMR and CD data of galanin in aqueous and nonaqueous solvents.

Molecular Dynamics with the United-Residue Model of Polypeptide Chains. I. Lagrange Equations of Motion and Tests of Numerical Stability in the Microcanonical Mode

“…Besides, the present U rot is one of the few terms remaining in UNRES that were derived as statistical potentials from the PDB. 36, 37 We are now working on replacing these statistical terms (including U rot ) with physics-based terms that will not depend on angles explicitly and will, therefore, not result in numerical instabilities in the forces. For this reason, instead of tuning the present integration scheme to handle the gradients of U rot perfectly, we worked out a practical temporary solution, which is described below.…”

“…[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] Each amino acid residue is represented by only two interaction sites, which makes the model simple enough to carry out large-scale simulations. In comparison to other mezoscopic protein models, UNRES offers two important advantages.…”

Full Optimization of Linear Parameters of a United Residue Protein Potential

“…Potential Energy Function. We use the UNRES force field, [24][25][26][27][28] where a polypeptide chain is represented by a sequence of R-carbon (C R ) atoms linked by virtual bonds with attached united side chains (SC) and united peptide groups (p) located in the middle between the consecutive C R s. All of the virtual bond lengths are fixed: the C R -C R distance is taken as 3.8 Å, and the C R -SC distances are given for each amino acid type. The energy of the chain is given by where the w's are the relative weights that were refined in earlier works.…”

“…The united residue (UNRES) potential is given by the expression [24][25][26][27][28] 1. Side-Chain Interactions.…”

“…The 10-55 fragment of staphylococcal protein A (1bdd) was used by Lee et al 23 to refine a coarse-grained potential called the UNRES potential, [24][25][26][27][28] where each residue is approximated by two interaction sites. This potential was successfully applied to the prediction of the unknown structures of proteins in CASP3, 17,29,30 and its basic version consists of seven interaction terms.…”