title: Genetic algorithm with alternating selection pressure for protein side-chain packing and pK(a) prediction.
abstract: The prediction of protein side-chain conformation is central for understanding protein functions. Side-chain packing is a sub-problem of protein folding and its computational complexity has been shown to be NP-hard. We investigated the capabilities of a hybrid (genetic algorithm/simulated annealing) technique for side-chain packing and for the generation of an ensemble of low energy side-chain conformations. Our method first relies on obtaining a near-optimal low energy protein conformation by optimizing its amino-acid side-chains. Upon convergence, the genetic algorithm is allowed to undergo forward and "backward" evolution by alternating selection pressures between minimal and higher energy setpoints. We show that this technique is very efficient for obtaining distributions of solutions centered at any desired energy from the minimum. We outline the general concepts of our evolutionary sampling methodology using three different alternating selective pressure schemes. Quality of the method was assessed by using it for protein pK(a) prediction.
authors.affiliation: Department of Computer Science, Brock University, 500 Glenridge Ave., St. Catharines, Ontario, Canada.
authors.forename: Pascal
authors.initials: P
authors.lastname: Comte
authors.forename: Sergei
authors.initials: S
authors.lastname: Vassiliev
authors.forename: Sheridan
authors.initials: S
authors.lastname: Houghten
authors.forename: Doug
authors.initials: D
authors.lastname: Bruce
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D004529:Egg White / Q000737:chemistry; D019143:Evolution, Molecular; D008957:Models, Genetic; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D011506:Proteins; D009113:Muramidase