Residue-Specific Force Field Based on Protein Coil
Library. RSFF2: Modification of AMBER ff99SB
- Publication date
- Publisher
Abstract
Recently, we developed a residue-specific
force field (RSFF1) based
on conformational free-energy distributions of the 20 amino acid residues
from a protein coil library. Most parameters in RSFF1 were adopted
from the OPLS-AA/L force field, but some van der Waals and torsional
parameters that effectively affect local conformational preferences
were introduced specifically for individual residues to fit the coil
library distributions. Here a similar strategy has been applied to
modify the Amber ff99SB force field, and a new force field named RSFF2
is developed. It can successfully fold α-helical structures
such as polyalanine peptides, Trp-cage miniprotein, and villin headpiece
subdomain and β-sheet structures such as Trpzip-2, GB1 β-hairpins,
and the WW domain, simultaneously. The properties of various popular
force fields in balancing between α-helix and β-sheet
are analyzed based on their descriptions of local conformational features
of various residues, and the analysis reveals the importance of accurate
local free-energy distributions. Unlike the RSFF1, which overestimates
the stability of both α-helix and β-sheet, RSFF2 gives
melting curves of α-helical peptides and Trp-cage in good agreement
with experimental data. Fitting to the two-state model, RSFF2 gives
folding enthalpies and entropies in reasonably good agreement with
available experimental results