Improved fragment-based protein structure prediction by redesign of search heuristics.

ABSTRACT: Difficulty in sampling large and complex conformational spaces remains a key limitation in fragment-based de novo prediction of protein structure. Our previous work has shown that even for small-to-medium-sized proteins, some current methods inadequately sample alternative structures. We have developed two new conformational sampling techniques, one employing a bilevel optimisation framework and the other employing iterated local search. We combine strategies of forced structural perturbation (where some fragment insertions are accepted regardless of their impact on scores) and greedy local optimisation, allowing greater exploration of the available conformational space. Comparisons against the Rosetta Abinitio method indicate that our protocols more frequently generate native-like predict

SUBMITTER: Kandathil SM 

PROVIDER: S-EPMC6135816 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature