Consistent free energy landscapes and thermodynamic properties of small proteins based on a single all-atom force field employing an implicit solvation.
We have attempted to improve the PARAM99 force field in conjunction with the generalized Born (GB) solvation model with a surface area correction for more consistent protein folding simulations. For this purpose, using an extended alphabeta training set of five well-studied molecules with various folds (alpha, beta, and betabetaalpha), a previously modified version of PARAM99/GBSA is further refined, such that all native states of the five training species correspond to their lowest free energy minimum states. The resulting modified force field (PARAM99MOD5/GBSA) clearly produces reasonably acceptable conformational free energy surfaces of the training set with correct identifications of their native states in the free energy minimum states. Moreover, due to its well-balanced nature, this new force field is expected to describe secondary structure propensities of diverse folds in a more consistent manner. Remarkably, temperature dependent behaviors simulated with the current force field are in good agreement with the experiment. This agreement is a significant improvement over the existing standard all-atom force fields. In addition, fundamentally important thermodynamic quantities, such as folding enthalpy (DeltaH) and entropy (DeltaS), agree reasonably well with the experimental data.
Kim
Eunae
E
Department of Chemistry, Pusan National University, Busan 609-735, Korea.
Jang
Soonmin
S
Pak
Youngshang
Y
D004735:Energy Transfer; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics; D013997:Time Factors
D011506:Proteins; D012997:Solvents