Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Conformational Behavior of Short Peptides in Explicit Solvent Simulations
Peptides are important mediators in the regulation of many physiological processes, eliciting actions as hormones, neurotransmitters or immunomodulators. Moreover, peptides also function as mediators of protein-protein interactions, acting as surrogates of protein epitopes. Their wide range of activities is associated with their structural features as well as their complementary with the corresponding receptors. Accordingly a deep knowledge of their structural behavior is important to understand their biological activities and is pivotal for designing new peptide surrogates or peptidomimetics that may render new applications and open new frontiers.
In contrast to most proteins that exhibit a native structure in solution, the structure of short peptides is commonly associated to a random coil. This can be explained in terms of their flexible nature at room temperature that in turn, is a consequence of the dynamic equilibrium between different conformational states. Thus, the conformational profile shown in solution is in fact an average picture of the structural features of the different states of an ensemble. This concept has also been supported experimentally, challenging the paradigm of random coils for the idea that peptides exhibit local structural features (Schweitzer-Stenner ,2012).
The available conformational states of a peptide are the result of the balance between interactions between the atoms of the peptide (intramolecular) and interactions of the peptide atoms with molecules of the environment (intermolecular). The former dictate the intrinsic conformational features of the peptide that are associated to its amino acid sequence, whereas the latter modify this intrinsic conformational profile and the ensemble distribution.
The application of computational methods to characterize the set of accessible conformations of a peptide at room temperature requires a thorough search of the energy surface. However, this is a difficult task due to its rugged nature with many low energy conformations and barriers that, becomes even more demanding when the peptide is modeled soaked in a box of solvent molecules. In the present communication we present the results of thorough searches of the conformational space of diverse peptides to discuss the performance of the methodology as well as the insights gathered on the conformational behavior of peptides in terms of intrinsic conformational features and the effect of the solvent.
R. Schweitzer-Stenner (2012). Conformational propensities and residual structures in unfolded peptides and proteins. Mol BioSyst 8, 122-133.
Juan Jesus Perez
Department of Chemical Engineering