Comparing folding codes in simple heteropolymer models of protein evolutionary landscape: robustness of the superfunnel paradigm.
Understanding the evolution of biopolymers is a key element in rationalizing their structures and functions. Simple exact models (SEMs) are well-positioned to address general principles of evolution as they permit the exhaustive enumeration of both sequence and structure (conformational) spaces. The physics-based models of the complete mapping between genotypes and phenotypes afforded by SEMs have proven valuable for gaining insight into how adaptation and selection operate among large collections of sequences and structures. This study compares the properties of evolutionary landscapes of a variety of SEMs to delineate robust predictions and possible model-specific artifacts. Among the models studied, the ruggedness of evolutionary landscape is significantly model-dependent; those derived from more protein-like models appear to be smoother. We found that a common practice of restricting protein structure space to maximally compact lattice conformations results in (i.e., "designs in") many encodable (designable) structures that are not otherwise encodable in the corresponding unrestrained structure space. This discrepancy is especially severe for model potentials that seek to mimic the major role of hydrophobic interactions in protein folding. In general, restricting conformations to be maximally compact leads to larger changes in the model genotype-phenotype mapping than a moderate shifting of reference state energy of the model potential function to allow for more specific encoding via the "designing out" effects of repulsive interactions. Despite these variations, the superfunnel paradigm applies to all SEMs we have tested: For a majority of neutral nets across different models, there exists a funnel-like organization of native stabilities for the sequences in a neutral net encoding for the same structure, and the thermodynamically most stable sequence is also the most robust against mutation.
Wroe
Richard
R
Faculty of Life Sciences, University of Manchester, United Kingdom.
Bornberg-Bauer
Erich
E
Chan
Hue Sun
HS
D001703:Biophysics / Q000379:methods*; D001704:Biopolymers / Q000737:chemistry*; D019143:Evolution, Molecular; D005838:Genotype; D008962:Models, Theoretical; D009154:Mutation; D010641:Phenotype; D011108:Polymers / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D040901:Proteomics / Q000379:methods*; D012984:Software; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D001704:Biopolymers; D011108:Polymers