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1. CHARMM‐GUI 10 years for biomolecular modeling and simulation

   https://doi.org/10.1002/jcc.24660  

   Jo, Sunhwan ; Cheng, Xi ; Lee, Jumin ; Kim, Seonghoon ; Park, Sang‐Jun ; Patel, Dhilon S. ; Beaven, Andrew H. ; Lee, Kyu Il ; Rui, Huan ; Park, Soohyung ; et al ( November 2016 , Journal of Computational Chemistry)

   CHARMM‐GUI,http://www.charmm-gui.org, is a web‐based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM‐GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM‐GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1)PDB Reader & Manipulator,Glycan Reader, andLigand Reader & Modelerfor reading and modifying molecules; (2)Quick MD Simulator,Membrane Builder,Nanodisc Builder,HMMM Builder,Monolayer Builder,Micelle Builder, andHex Phase Builderfor building all‐atom simulation systems in various environments; (3)PACE CG BuilderandMartini Makerfor building coarse‐grained simulation systems; (4)DEER FacilitatorandMDFF/xMDFF Utilizerfor experimentally guided simulations; (5)Implicit Solvent Modeler,PBEQ‐Solver, andGCMC/BD Ion Simulatorfor implicit solvent related calculations; (6)Ligand Binderfor ligand solvation and binding free energy simulations; and (7)Drude Prepperfor preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM‐GUI, such asGlycolipid Modelerfor generation of various glycolipid structures, andLPS Modelerfor generation of lipopolysaccharide structures from various Gram‐negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM‐GUI development project. © 2016 Wiley Periodicals, Inc.

    

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2. Isolated and solvated chiroptical behavior in conformationally flexible butanamines

   https://doi.org/10.1002/chir.23570  

   Lemler, Paul M. ; Craft, Clayton L. ; Pollok, Corina H. ; Regan, Thomas P. ; Vaccaro, Patrick H. ( June 2023 , Chirality)

   The nonresonant optical activity of two highly flexible aliphatic amines, (2R)‐3‐methyl‐2‐butanamine (R‐MBA) and (2R)‐(3,3)‐dimethyl‐2‐butanamine (R‐DMBA), has been probed under isolated and solvated conditions to examine the roles of conformational isomerism and to explore the influence of extrinsic perturbations. The optical rotatory dispersion (ORD) measured in six solvents presented uniformly negative rotatory powers over the 320–590 nm region, with the long‐wavelength magnitude of chiroptical response growing nearly monotonically as the dielectric constant of the surroundings diminished. The intrinsic specific optical rotation, (in deg dm⁻¹[g/mL]⁻¹), extracted for ambient vapor‐phase samples ofR‐MBA [−11.031(98) and −2.29 (11)] andR‐DMBA [−9.434 (72) and −1.350 (48)] at 355 and 633 nm were best reproduced by counterintuitive solvents of high polarity (yet low polarizability) like acetonitrile and methanol. Attempts to interpret observed spectral signatures quantitatively relied on the linear‐response frameworks of density‐functional theory (B3LYP, cam‐B3LYP, and dispersion‐corrected analogs) and coupled‐cluster theory (CCSD), with variants of the polarizable continuum model (PCM) deployed to account for the effects of implicit solvation. Building on the identification of several low‐lying equilibrium geometries (nine forR‐MBA and three forR‐DMBA), ensemble‐averaged ORD profiles were calculated atT = 300 K by means of the independent‐conformer ansatz, which enabled response properties predicted for the optimized structure of each isomer to be combined through Boltzmann‐weighted population fractions derived from corresponding relative internal‐energy or free‐energy values, the latter of which stemmed from composite CBS‐APNO and G4 analyses. Although reasonable accord between theory and experiment was realized for the isolated (vapor‐phase) species, the solution‐phase results were less satisfactory and tended to degrade progressively as the solvent polarity increased. These trends were attributed to solvent‐mediated changes in structural parameters and energy metrics for the transition states that separate and putatively isolate the equilibrium conformations supported by the ground electronic potential‐energy surface, with the resulting displacement of barrier locations and/or decrease of barrier heights compromising the underlying premise of the independent‐conformer ansatz.

    

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3. Non-covalent complexes of the peptide fragment Gly-Asn-Asn-Gln-Gln-Asn-Tyr in the gas-phase. Photodissociative cross-linking, Born–Oppenheimer molecular dynamics, and ab initio computational binding study

   https://doi.org/10.1039/c8cp06893c  

   Huang, Shu R. ; Liu, Yang ; Tureček, František ( January 2019 , Physical Chemistry Chemical Physics)

   Non-covalent complexes of the short amyloid peptide motif Gly-Asn-Asn-Gln-Gln-Asn-Tyr (GNNQQNY) with peptide counterparts that were tagged with a diazirine ring at the N-termini (*GNNQQNY) were generated as singly charged ions in the gas phase. Specific laser photodissociation (UVPD) of the diazirine tag in the gas-phase complexes at 355 nm generated transient carbene intermediates that underwent covalent cross-linking with the target GNNQQNY peptide. The crosslinking yields ranged between 0.8 and 4.5%, depending on the combinations of peptide C-terminal amides and carboxylates. The covalent complexes were analyzed by collision-induced dissociation tandem mass spectrometry (CID-MS 3 ), providing distributions of cross-links at the target peptide amino acid residues. A general preference for cross-linking at the target peptide Gln-4-Gln-5-Asn-6-Tyr-7 segment was observed. Born–Oppenheimer molecular dynamics calculations were used to obtain 100 ps trajectories for nine lowest free-energy conformers identified by ωB97X-D/6-31+G(d,p) gradient geometry optimizations. The trajectories were analyzed for close contacts between the incipient carbene atom and the X–H bonds in the target peptide. The close-contact analysis pointed to the Gln-5 and Tyr-7 residues as the most likely sites of cross-linking, consistent with the experimental CID-MS 3 results. Non-covalent binding in the amide complexes was evaluated by DFT calculations of structures and energies. Although antiparallel arrangements of the GNNQQNY and *GNNQQNY peptides were favored in low-energy gas-phase and solvated complexes, the conformations and peptide–peptide interface surfaces were found to differ from the secondary structure of the dry interface in GNNQQNY motifs of amyloid aggregates. 

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4. Determining gas-phase chelation of zinc, cadmium, and copper cations with HisHis dipeptide using action spectroscopy and theoretical calculations

   https://doi.org/10.1016/j.ijms.2023.117154  

   Stevenson, Brandon C. ; Berden, Giel ; Martens, Jonathan ; Oomens, Jos ; Armentrout, P.B. ( January 2024 , International Journal of Mass Spectrometry)

   Using light generated by an infrared free electron laser, action spectroscopy was performed on doubly charged complexes of the metalated dipeptide histidyl-histidine (HisHis). Metal cations used were zinc, cadmium, and copper. Molecular dynamics and quantum-chemical calculations were used to screen a large number of conformers, whose theoretical infrared spectra were compared to the recorded action spectra of these metalated complexes. The zinc and cadmium spectra display dominant features associated with an iminol binding motif of the HisHis ligand, where the metal ion coordinates with both pros () nitrogens of the imidazole sidechains, the terminal carbonyl oxygen, and the backbone nitrogen for which the hydrogen ordinarily bound here has migrated to a carbonyl. The copper complex was difficult to assign to a single species, because a few predicted bands are absent from the experimental spectrum. The theoretical single point energies were also calculated for all structures examined, and DFT methods were found to describe the ion conformer populations in the case of the zinc and cadmium chelates better than the MP2 prediction. 

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5. Coupling Monte Carlo, variational implicit solvation, and binary level-set for simulations of biomolecular binding

   Zhang, Z. ; Ricci, C. ; Fan, C. ; Cheng, L.-T. ; Li, B. ; McCammon, J.A. ( March 2021 , Journal of chemical theory and computation)

   null (Ed.)

   We develop a hybrid approach that combines the Monte Carlo (MC)method, a variational implicit-solvent model (VISM), and a binary level-set method forthe simulation of biomolecular binding in an aqueous solvent. The solvation free energy for the biomolecular complex is estimated by minimizing the VISM free-energy functional of all possible solute−solvent interfaces that are used as dielectric boundaries. This functional consists of the solute volumetric, solute−solvent interfacial, solute−solvent van der Waals interaction, and electrostatic free energy. A technique of shifting the dielectric boundary is used to accurately predict the electrostatic part of the solvation free energy.Minimizing such a functional in each MC move is made possible by our new and fast binary level-set method. This method is based on the approximation of surface area by the convolution of an indicator function with a compactly supported kernel and is implemented by simple flips of numerical grid cells locally around the solute−solvent interface. We apply our approach to the p53-MDM2 system for which the two molecules are approximated by rigid bodies. Our efficient approach captures some of the poses before the final bound state. All atom molecular dynamics simulations with most of such poses quickly reach the final bound state.Our work is a new step toward realistic simulations of biomolecular interactions. With further improvement of coarse graining and MC sampling, and combined with other models, our hybrid approach can be used to study the free-energy landscape and kinetic pathways of ligand binding to proteins. 

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