Doğal halde olmayan peptitlerin konformasyonlari: Kabataslak model gösterimi

The native structure of proteins is stabilized by both local and non-local interactions. The available phase space is highly reduced in size due to the local interactions, but non-local interactions determine the final, physiologically active native structure. Although it is wellknown that these two types of interactions are the key factors in determining the tertiary structure, their relative contributions is open for debate. This study will lay the groundwork for the investigation of relative contributions of these interactions. The contribution of both local and non-local neighbors to the Ramachandran map of the residue in question is examined by using statistical weight matrices (U) constructed according to the Markov assumption. An efficient matrix multiplication scheme based on rotational isomeric states model is introduced for studying realistic conformations of homotripeptides of all-alanine, tryptophan, valine, and tyrosine and AXA tripeptides, where X represents alanine, valine, tryptophan, and tyrosine in the unfolded state. This scheme is based on U?s obtained from mono and dipeptide molecular dynamics simulations. By using these matrices one can obtain the Ramachandran map of the central residue of longer sequences, such as tripeptides. Comparison of explicit tripeptide simulations with the Markov model shows that the Markov assumption fails to capture interactions specific to the tripeptide. Here, a systematic correction is proposed for efficient calculation of realistic protein conformations. Preliminary results suggest that the Markov assumption can be improved significantly by adding the contributions from hydrogen bonds, which are only present in the tripeptide sequences. Such a coarse-grained model, Modified Markov model, will help elucidate the protein folding problem and improve secondary structure prediction algorithms.