title: Statistical theory of combinatorial libraries of folding proteins: energetic discrimination of a target structure.
abstract: A self-consistent theory is presented that can be used to estimate the number and composition of sequences satisfying a predetermined set of constraints. The theory is formulated so as to examine the features of sequences having a particular value of Delta=E(f)-<E>(u), where E(f) is the energy of sequences when in a target structure and <E>(u) is an average energy of non-target structures. The theory yields the probabilities w(i)(alpha) that each position i in the sequence is occupied by a particular monomer type alpha. The theory is applied to a simple lattice model of proteins. Excellent agreement is observed between the theory and the results of exact enumerations. The theory provides a quantitative framework for the design and interpretation of combinatorial experiments involving proteins, where a library of amino acid sequences is searched for sequences that fold to a desired structure.
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zou
authors.forename: J G
authors.initials: JG
authors.lastname: Saven
mesh_terms: D000595:Amino Acid Sequence; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D008958:Models, Molecular; D008962:Models, Theoretical; D019151:Peptide Library; D011108:Polymers; D011336:Probability; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D013223:Statistics as Topic; D013816:Thermodynamics
chemical_list: D019151:Peptide Library; D011108:Polymers; D011506:Proteins