Peptide Suboptimal Conformation Sampling for the Prediction of Protein-Peptide Interactions.

The blind identification of candidate patches of interaction on the protein surface is a difficult task that can hardly be accomplished without a heuristic or the use of simplified representations to speed up the search. The PEP-SiteFinder protocol performs a systematic blind search on the protein surface using a rigid docking procedure applied to a limited set of peptide suboptimal conformations expected to approximate satisfactorily the conformation of the peptide in interaction. All steps rely on a coarse-grained representation of the protein and the peptide.

A critical assessment of hidden markov model sub-optimal sampling strategies applied to the generation of peptide 3D models.

Hidden Markov Model derived structural alphabets are a probabilistic framework in which the complete conformational space of a peptidic chain is described in terms of probability distributions that can be sampled to identify conformations of largest probabilities. Here, we assess how three strategies to sample sub-optimal conformations-Viterbi k-best, forward backtrack and a taboo sampling approach-can lead to the efficient generation of peptide conformations. We show that the diversity of sampling is essential to compensate biases introduced in the estimates of the probabilities, and we find that only the forward backtrack and a taboo sampling strategies can efficiently generate native or near-native models.

PEP-FOLD3: faster de novo structure prediction for linear peptides in solution and in complex.

Structure determination of linear peptides of 5-50 amino acids in aqueous solution and interacting with proteins is a key aspect in structural biology. PEP-FOLD3 is a novel computational framework, that allows both (i) de novo free or biased prediction for linear peptides between 5 and 50 amino acids, and (ii) the generation of native-like conformations of peptides interacting with a protein when the interaction site is known in advance. PEP-FOLD3 is fast, and usually returns solutions in a few minutes.

De novo peptide structure prediction: an overview.

Peptide structure identification is an important contribution to the further characterization of the residues involved in functional interactions. De novo structure peptide prediction has, in the past few years, made significant progresses that make reasonable, for peptides up to 50 amino acids, its use for the fast identification of their structural topologies. Here, we introduce some of the concepts underlying approaches of the field, together with their limits.

PEP-SiteFinder: a tool for the blind identification of peptide binding sites on protein surfaces.

Peptide-protein interactions are important to many processes of life, particularly for signal transmission or regulatory mechanisms. When no information is known about the interaction between a protein and a peptide, it is of interest to propose candidate sites of interaction at the protein surface, to assist the design of biological experiments to probe the interaction, or to serve as a starting point for more focused in silico approaches. PEP-SiteFinder is a tool that will, given the structure of a protein and the sequence of a peptide, identify protein residues predicted to be at peptide-protein interface.