Dataset Information

Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo.

ABSTRACT: The binding between a peptide and a major histocompatibility complex (MHC) is one of the most important processes for the induction of an adaptive immune response. Many algorithms have been developed to predict peptide/MHC (pMHC) binding. However, no approach has yet been able to give structural insight into how peptides detach from the MHC.In this study, we used a combination of coarse graining, hierarchical natural move Monte Carlo and stochastic conformational optimization to explore the detachment processes of 32 different peptides from HLA-A*02:01. We performed 100 independent repeats of each stochastic simulation and found that the presence of experimentally known anchor amino acids affects the detachment trajectories of our peptides. Comparison with experimental binding affinity data indicates the reliability of our approach (area under the receiver operating characteristic curve 0.85). We also compared to a 1000?ns molecular dynamics simulation of a non-binding peptide (AAAKTPVIV) and HLA-A*02:01. Even in this simulation, the longest published for pMHC, the peptide does not fully detach. Our approach is orders of magnitude faster and as such allows us to explore pMHC detachment processes in a way not possible with all-atom molecular dynamics simulations.The source code is freely available for download at http://www.cs.ox.ac.uk/mosaics/.bernhard.knapp@stats.ox.ac.ukSupplementary data are available at Bioinformatics online.

SUBMITTER: Knapp B

PROVIDER: S-EPMC4708099 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo.

Knapp Bernhard B Demharter Samuel S Deane Charlotte M CM Minary Peter P

Bioinformatics (Oxford, England) 20150922 2

<h4>Motivation</h4>The binding between a peptide and a major histocompatibility complex (MHC) is one of the most important processes for the induction of an adaptive immune response. Many algorithms have been developed to predict peptide/MHC (pMHC) binding. However, no approach has yet been able to give structural insight into how peptides detach from the MHC.<h4>Results</h4>In this study, we used a combination of coarse graining, hierarchical natural move Monte Carlo and stochastic conformation ...[more]

PMID: 26395770

Similar Datasets

Project description:In this work, we present a robust and powerful method for the verification, with arbitrary accuracy, of Monte Carlo codes for simulating random walks in complex media. Such random walks are typical of photon propagation in turbid media, scattering of particles, i.e., neutrons in a nuclear reactor or animal/humans' migration. Among the numerous applications, Monte Carlo method is also considered a gold standard for numerically "solving" the scalar radiative transport equation even in complex geometries and distributions of the optical properties. In this work, we apply the verification method to a Monte Carlo code which is a forward problem solver extensively used for typical applications in the field of tissue optics. The method is based on the well-known law of average path length invariance when the entrance of the entities/particles in a medium obeys to a simple cosine law, i.e., Lambertian entrance, and annihilation of particles inside the medium is absent. By using this law we achieve two important points: (1) the invariance of the average path length guarantees that the expected value is known regardless of the complexity of the medium; (2) the accuracy of a Monte Carlo code can be assessed by simple statistical tests. We will show that we can reach an arbitrary accuracy of the estimated average pathlength as the number of simulated trajectories increases. The method can be applied in complete generality versus the scattering and geometrical properties of the medium, as well as in presence of refractive index mismatches in the optical case. In particular, this verification method is reliable to detect inaccuracies in the treatment of boundaries of finite media. The results presented in this paper, obtained by a standard computer machine, show a verification of our Monte Carlo code up to the sixth decimal digit. We discuss how this method can provide a fundamental tool for the verification of Monte Carlo codes in the geometry of interest, without resorting to simpler geometries and uniform distribution of the scattering properties.

Project description:We implement a Monte Carlo heuristic algorithm to model drug release from a solid dosage form. We show that with Monte Carlo simulations it is possible to identify and explain the causes of the unsatisfactory predictive power of current drug release models. It is well known that the power-law, the exponential models, as well as those derived from or inspired by them accurately reproduce only the first 60% of the release curve of a drug from a dosage form. In this study, by using Monte Carlo simulation approaches, we show that these models fit quite accurately almost the entire release profile when the release kinetics is not governed by the coexistence of different physico-chemical mechanisms. We show that the accuracy of the traditional models are comparable with those of Monte Carlo heuristics when these heuristics approximate and oversimply the phenomenology of drug release. This observation suggests to develop and use novel Monte Carlo simulation heuristics able to describe the complexity of the release kinetics, and consequently to generate data more similar to those observed in real experiments. Implementing Monte Carlo simulation heuristics of the drug release phenomenology may be much straightforward and efficient than hypothesizing and implementing from scratch complex mathematical models of the physical processes involved in drug release. Identifying and understanding through simulation heuristics what processes of this phenomenology reproduce the observed data and then formalize them in mathematics may allow avoiding time-consuming, trial-error based regression procedures. Three bullet points, highlighting the customization of the procedure. •An efficient heuristics based on Monte Carlo methods for simulating drug release from solid dosage form encodes is presented. It specifies the model of the physical process in a simple but accurate way in the formula of the Monte Carlo Micro Step (MCS) time interval.•Given the experimentally observed curve of drug release, we point out how Monte Carlo heuristics can be integrated in an evolutionary algorithmic approach to infer the mode of MCS best fitting the observed data, and thus the observed release kinetics.•The software implementing the method is written in R language, the free most used language in the bioinformaticians community.

Dataset Information

Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo.

Publications

Exploring peptide/MHC detachment processes using hierarchical natural move Monte Carlo.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets