A coarse-grained alpha-carbon protein model with anisotropic hydrogen-bonding.
We develop a sequence based alpha-carbon model to incorporate a mean field estimate of the orientation dependence of the polypeptide chain that gives rise to specific hydrogen bond pairing to stabilize alpha-helices and beta-sheets. We illustrate the success of the new protein model in capturing thermodynamic measures and folding mechanism of proteins L and G. Compared to our previous coarse-grained model, the new model shows greater folding cooperativity and improvements in designability of protein sequences, as well as predicting correct trends for kinetic rates and mechanism for proteins L and G. We believe the model is broadly applicable to other protein folding and protein-protein co-assembly processes, and does not require experimental input beyond the topology description of the native state. Even without tertiary topology information, it can also serve as a mid-resolution protein model for more exhaustive conformational search strategies that can bridge back down to atomic descriptions of the polypeptide chain.
Yap
Eng-Hui
EH
UCSF/UCB Joint Graduate Group in Bioengineering, Berkeley, California 94720, USA.
Fawzi
Nicolas Lux
NL
Head-Gordon
Teresa
T
D000595:Amino Acid Sequence; D003198:Computer Simulation; D006860:Hydrogen Bonding; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
D011506:Proteins