Proteins structure, evaluation

Knowledge-based functions are based on the derivation of statistical preferences in the form of potentials for protein ligand atom pair interactions. Similar to potentials derived for protein folding and protein structure evaluation (e.g., Ref. 148), pair potentials akin to potentials of mean force (PMFs) are derived for various protein and ligand atom types using the PDB as a knowledge base. The PMF scoring function [118]... 

Cuff IA and G J Barton 1999. Evaluation and Improvement of Multiple Sequence Methods for P Secondary Structure Prediction. Proteins Structure, Function and Genetics 34 508-519. 

Kramer B, M Rarey and T Lengauer 1999. Evaluation of the FLEXX Incremental Constructioi Algorithm for Protein-Ligand Docking. Proteins Structure, Function and Genetics 37 228-241. 

TF Flavel. An evaluation of computational strategies for use m the determination of protein structure from distance constraints obtained by nuclear magnetic resonance. Prog Biophys Mol Biol 56 43, 1991. 

Eortunately, a 3D model does not have to be absolutely perfect to be helpful in biology, as demonstrated by the applications listed above. However, the type of question that can be addressed with a particular model does depend on the model s accuracy. At the low end of the accuracy spectrum, there are models that are based on less than 25% sequence identity and have sometimes less than 50% of their atoms within 3.5 A of their correct positions. However, such models still have the correct fold, and even knowing only the fold of a protein is frequently sufficient to predict its approximate biochemical function. More specifically, only nine out of 80 fold families known in 1994 contained proteins (domains) that were not in the same functional class, although 32% of all protein structures belonged to one of the nine superfolds [229]. Models in this low range of accuracy combined with model evaluation can be used for confirming or rejecting a match between remotely related proteins [9,58]. 

R Sanchez, A Sail. Evaluation of comparative protein structure modeling by MODELLER-3. Pi otems Suppl 1 50-58, 1997. 

L Chiche, LM Gregoret, FE Cohen, PA Kollman. Protein model structure evaluation using the solvation free energy of folding. Proc Natl Acad Sci USA 87 3240-3244, 1990. 

MAS Saqi, PA Bates, MJE Sternberg. Towards an automatic method of predicting protein structure by homology An evaluation of suboptimal sequence alignments. Protein Eng 5 305-311, 1992. 

The essential distinction between the approaches used to formulate and evaluate proteins, compared with conventional low molecular weight drugs, lies in the need to maintain several levels of protein structure and the unique chemical and physical properties that these higher-order structures convey. Proteins are condensation polymers of amino acids, joined by peptide bonds. The levels of protein architecture are typically described in terms of the four orders of structure [23,24] depicted in Fig. 2. The primary structure refers to the sequence of amino acids and the location of any disulfide bonds. Secondary structure is derived from the steric relations of amino acid residues that are close to one another. The alpha-helix and beta-pleated sheet are examples of periodic secondary structure. Tertiary... 

Prosite is perhaps the best known of the domain databases (Hofmann et al., 1999). The Prosite database is a good source of high quality annotation for protein domain families. Prosite documentation includes a section on the functional meaning of a match to the entry and a list of example members of the family. Prosite documentation also includes literature references and cross links to other databases such as the PDB collection of protein structures (Bernstein et al., 1977). For each Prosite document, there is a Prosite pattern, profile, or both to detect the domain family. The profiles are the most sensitive detection method in Prosite. The Prosite profiles provide Zscores for matches allowing statistical evaluation of the match to a new protein. Profiles are now available for many of the common protein domains. Prosite profiles use the generalized profile software (Bucher et al., 1996). 

In order to evaluate the occurrence and distinctness of the major turn types as found empirically in protein structures, Figs. 35 through... 

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