Coarse-Grained Lattice Model Simulations of Sequence-Structure Fitness of a Ribosome-Inactivating Protein
Abstract
Many realistic protein-engineering design problems extend beyond the computational limits of what is considered practical when applying all-atom molecular dynamics simulation methods. Lattice models provide computationally robust alternatives, yet most are regarded as too simplistic to accurately capture the details of complex designs. We revisit a coarse-grained lattice simulation model and demonstrate that a multiresolution modeling approach of reconstructing all-atom structures from lattice chains is of sufficient accuracy to resolve the comparability of sequence-structure modifications of the ricin A-chain (RTA) protein fold. For a modeled structure, the unfolding-folding transition temperature was calculated from the heat capacity using either the potential energy from the lattice model or the all-atom CHARMM19 force-field plus a generalized Born solvent approximation. We found, that despite the low-resolution modeling of conformational states, the potential energy functions were capable of detecting the relative change in the thermodynamic transition temperature that distinguishes between a protein design and the native RTA fold in excellent accord with reported experimental studies of thermal denaturation. A discussion is provided of different sequences fitted to the RTA fold and a possible unfolding model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 05, 2007
- Accession Number
- ADA593508
Entities
People
- In-Chul Yeh
- Mark A Olson
- Michael S. Lee
Organizations
- United States Army Research Laboratory