Development of a Coarse –Grained Model, and Its Application to Free Energy Studies In Proteins

Simplified Coarse Grained protein models have been in use since 1975 and are being used extensively in folding studies. In this work, we provide a brief description of our Coarse Grained (CG) model and present its application on the free energy calculations of large biological systems. This model has been recently used for the study of the free energy associated with transmembrane (TM) helices insertions (Rychkova et al, PNAS 107,17598-17603). Our CG model, after recent modifications for the calculation of electrostatic interactions, was used for the study of TM/translocon system even though the structural characteristics are still not clear. The CG model has been used for the study of voltage activated ion channels. Meaningful converging microscopic simulations for ion channels are not yet available and macroscopic treatments involve major uncertainties in key features. The CG model has been extended, in order to perform simulations of membrane/protein systems under external potential (Dryga et al, BBA, under preparation). Finally, the CG model shows promising results, when used for the calculation of protein folding energies ΔG_fold and changes of folding energies upon mutations ΔΔG.