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Abstract A generalized understanding of protein dynamics is an unsolved scientific problem, the solution of which is critical to the interpretation of the structure-function relationships that govern essential biological processes. Here, we approach this problem by constructing coarse-grained molecular potentials based on artificial neural networks and grounded in statistical mechanics. For training, we build a unique dataset of unbiased all-atom molecular dynamics simulations of approximately 9 ms for twelve different proteins with multiple secondary structure arrangements. The coarse-grained models are capable of accelerating the dynamics by more than three orders of magnitude while preserving the thermodynamics of the systems. Coarse-grained simulations identify relevant structural states in the ensemble with comparable energetics to the all-atom systems. Furthermore, we show that a single coarse-grained potential can integrate all twelve proteins and can capture experimental structural features of mutated proteins. These results indicate that machine learning coarse-grained potentials could provide a feasible approach to simulate and understand protein dynamics. 

The accurate prediction of protein-ligand binding affinities is crucial for drug discovery. Alchemical free energy calculations have become a popular tool for this purpose. However, the accuracy and reliability of these methods can vary depending on the methodology. In this study, we evaluate the performance of a relative binding free energy protocol based on the alchemical transfer method (ATM), a novel approach based on a coordinate transformation that swaps the positions of two ligands. The results show that ATM matches the performance of more complex free energy perturbation (FEP) methods in terms of Pearson correlation, but with marginally higher mean absolute errors. This study shows that the ATM method is competitive compared to more traditional methods in speed and accuracy and offers the advantage of being applicable with any potential energy function. 

Measurements are presented of the cross-section for the central exclusive production ofJ/\psi\to\mu^+\mu^- $J/\psi \to {\mu }^{+}{\mu }^{-}$and\psi(2S)\to\mu^+\mu^- $\psi \left(2S\right)\to {\mu }^{+}{\mu }^{-}$processes in proton-proton collisions at\sqrt{s} = 13 \ \mathrm{TeV} $\sqrt{s}=13TeV$with 2016–2018 data. They are performed by requiring both muons to be in the LHCb acceptance (with pseudorapidity2<\eta_{\mu^±} < 4.5 $2<{\eta }_{{\mu }^{\pm }}<4.5$) and mesons in the rapidity range2.0 < y < 4.5 $2.0<y<4.5$. The integrated cross-section results are\sigma_{J/\psi\to\mu^+\mu^-}(2.0 ${\sigma }_{J/\psi \to {\mu }^{+}{\mu }^{-}}(2.0<y_{J/\psi }<4.5,2.0<{\eta }_{{\mu }^{\pm }}<4.5)=400\pm 2\pm 5\pm 12pb,{\sigma }_{\psi \left(2S\right)\to {\mu }^{+}{\mu }^{-}}(2.0<y_{\psi \left(2S\right)}<4.5,2.0<{\eta }_{{\mu }^{\pm }}<4.5)=9.40\pm 0.15\pm 0.13\pm 0.27pb,$where the uncertainties are statistical, systematic and due to the luminosity determination. In addition, a measurement of the ratio of\psi(2S) $\psi \left(2S\right)$andJ/\psi $J/\psi$cross-sections, at an average photon-proton centre-of-mass energy of1\ \mathrm{TeV} $1TeV$, is performed, giving$ = 0.1763 ± 0.0029 ± 0.0008 ± 0.0039,$$ where the first uncertainty is statistical, the second systematic and the third due to the knowledge of the involved branching fractions. For the first time, the dependence of theJ/\psi$ $J/\psi$and\psi(2S) $\psi \left(2S\right)$cross-sections on the total transverse momentum transfer is determined inpp $pp$collisions and is found consistent with the behaviour observed in electron-proton collisions.