196,395 research outputs found
Towards bulk thermodynamics via non-equilibrium methods: gaseous methane as a case study
No full textWe illustrate how the Jarzynski equality (JE), which is the progenitor of non-equilibrium methods aimed at constructing free energy landscapes for molecular-sized fluctuating systems subjected to steered transformations, can be applied to derive equations of state for bulk systems. The key-step consists of physically framing the computational strategy of "total energy morphing'', recently presented by us as an efficient implementation of the JE [M. Zerbetto, A. Piserchia, D. Frezzato, J. Comput. Chem., 2014, 35, 1865-1881], in terms of build-up of the real thermodynamic state of a bulk material from the corresponding ideal state, in which the particles are non-interacting. In this context, the JE machinery yields the excess free energy versus suitably chosen controlled state variables, whose thermodynamic derivatives eventually lead to the equation of state. As an explanatory case study, we apply the methodology to derive the equation of state of gaseous methane by constructing the Helmholtz free energy versus the particle density (at fixed temperature) and then evaluating the thermodynamic derivative with respect to the volume. In our intent, this "old-style'' work on gaseous methane should open the way for the investigation of thermodynamics of extended systems via non-equilibrium methods
QSLE-v1.0: A New Software Package for the Calculation of Coupled Quantum-Classical Dynamics in Condensed Phases Based on a Stochastic Approach
No full textRecently, a stochastic version of the quantum-classical Liouville equation has been proposed [Campeggio, J.; Cortivo, R.; Zerbetto, M. J. Chem. Phys. 2023, 158, 244104], to compute the coupled quantum-classical dynamics of molecules in condensed phases. The approach, called quantum-stochastic Liouville equation (QSLE), is based on coupling the time evolution of electronic states to a stochastic description of the relevant (classical) nuclear coordinates. Natural internal coordinates are used, i.e., bond lengths, bond angles, and dihedral angles. The approach is tailored to directly propagate the populations of the electronic states over time, based on a classical Fokker-Planck equation for the nuclear degrees of freedom coupled to a master equation for the jumps among the electronic states. The QSLE is a multiscale approach requiring many ingredients to be assembled in order to carry out the numerical solution. To make the approach accessible, a software package that handles the main (and most cumbersome) details of the numerical workflow has been implemented into the software package QSLE-v1.0, which is introduced in the present paper. Here, it is considered the case of one torsional nuclear coordinate and two nonadiabatic electronic potential energy surfaces. This is a very basic model for interpreting photoisomerization or charge transfer phenomena, but despite its simplicity, it can be applied even in complex systems where the relevant quantum/classical parts affecting the phenomena under study are highly localized. A sand-box model system for describing photoisomerization processes is reported to demonstrate the usage of the software package. QSLE-v1.0 is open source and distributed under the GPLv2.0 license
Modeling regulation of transcription initiation
No full textThe concept of activation in transcriptional regulation is based on the assumption that product mRNA increases monotonically as a function of regulator concentration. We analyze the Shea-Ackers model of transcription and find this assumption to be correct only for the simplest of promoters. We define a new regulatory constant that is a nonlinear combination of association and transcription initiation constants characterizing activation and repression for more complicated promoters. Our results can guide the synthesis of new promoters and lead to a deeper understanding of the constraints guiding the natural promoters evolution. Using a validated mathematical model based on the Shea-Ackers transcription rate function, we then show that two modes of upregulation have very different effects on the function of promoter PRM in phage lambda. We predict that if CI2 bound to OR2 produced equal increase in RNAP-DNA binding constant (compared to wild-type increase in the closed-open transition probability), the lysogen would be significantly less stable. We then focus on the promoter clearance process during transcription initiation. Our work builds upon an initial sequence-dependent three-pathway model proposed by Xue et al. After making several modifications to this model and not being able to satisfactorily match experimental data, we introduce a new parameter to the model: the possible formation of secondary structure in the single stranded scrunched DNA accumulated before RNA polymerase is able to escape the promoter .Ph. D.Includes bibliographical referencesIncludes vitaby Eliane Zerbetto Trald
Insights on the supramolecular polymorphism of poly(γ-benzyl-L-glutamate) rod-like peptides from atomistic molecular dynamics simulations
No full textThis work reports an all-atom molecular dynamics study of the first stages of aggregation of poly(γ-benzyl-L-glutamate)—PBLG—polymers end-capped with C60. PBLG self-assembles in water and shows polymorphism when specific changes in the molecular structure are made. Three variants of PBLG are compared, which differ for the location of the C60 moiety: N-terminus, C-terminus, or both. The aim of the computational experiments was to rationalize the key molecular properties that are relevant to the supramolecular polymorphism. Single-peptide simulations in tetrahydrofuran and in water allowed to quantify the strength of the self-assembly driving force in terms of the overall order parameter of the phenyl rings that are “coating” the peptides. Two-peptide simulations for the singly capped peptides showed that two kinds of aggregates can be formed: one “slow” thermodynamically more stable, and one “fast” kinetically favoured. These first-stage aggregates are interpreted as the seeds leading to different self-assemblies. Graphical abstract: [Figure not available: see fulltext.
Polaritonic Chemistry: Hindering and Easing Ground State Polyenic Isomerization via Breakdown of σ-π Separation
No full textThe ground state conformational isomerization in polyenes is a symmetry allowed process. Its low energy barrier is governed by electron density transfer from the formal single bond that is rotated to the nearby formal double bonds. Along the reaction pathway, the transition state is therefore destabilized. The rules of polaritonic chemistry, i.e., chemistry in a nanocavity with reflecting windows, are barely beginning to be laid out. The standing electric field of the nanocavity couples strongly with the molecular wave function and modifies the potential energy curve in unexpected ways. A quantum electrodynamics approach, applied to the torsional degree of freedom of the central bond of butadiene, shows that formation of the polariton mixes the sigma-pi frameworks thereby stabilizing/destabilizing the planar, reactant-like conformations. The values of the fundamental mode of the cavity field used in the absence of the cavity do not trigger this mechanism
Life's Ratchet. How Molecular Machines Extract Order from Chaos
No full textReview of the book Life's Ratchet. How Molecular Machines Extract Order from Chaos by Peter M. Hoffman
Fullerene sorting proteins
No full textProteins bind fullerenes. Hydrophobic pockets can accommodate a carbon cage either in full or in part. However, the identification of proteins able to discriminate between different cages is an open issue. Prediction of candidates able to perform this function is desirable and is achieved with an inverse docking procedure that accurately accounts for (i) van der Waals interactions between the cage and the protein surface, (ii) desolvation free energy, (iii) shape complementarity, and (iv) minimization of the number of steric clashes through conformational variations. A set of more than 1000 protein structures is divided into four categories that either select C(60) or C(70) (p-C(60) or p-C(70)) and either accommodate the cages in the same pocket (homosaccic proteins, from σακκoζ meaning pocket) or in different pockets (heterosaccic proteins). In agreement with the experiments, the KcsA Potassium Channel is predicted to have one of the best performances for both cages. Possible ways to exploit the results and efficiently separate the two cages with proteins are also discussed
In Silico Carborane Docking to Proteins and Potential Drug Targets
No full textThe presence of boron atoms has made carboranes, C2B10H12, attractive candidates for boron neutron capture therapy. Because of their chemistry and possible conjugation with proteins, they can also be used to enhance interactions between pharmaceuticals and their targets and to increase the in vivo stability and bioavailability of compounds that are normally metabolized rapidly. Carboranes are isosteric to a rotating phenyl group, which they can substitute successfully in biologically active systems. A reverse ligand–protein docking approach was used in this work to identify binding proteins for carboranes. The screening was carried out on the drug target database PDTD that contains 1207 entries covering 841 known potential drug targets with structures taken from the Protein Data Bank. First, for validation, the protocol was applied to three crystal structures of proteins in which carborane derivatives are present. Then, the model was applied to systems for which the protein structure is available, but the binding site of carborane has not been reported. These systems were used for further validation of the protocol, while simultaneously providing new insight into the interactions between cage and protein. Finally, the screening was carried out on the database to reveal potential carborane binding targets of interest for biological and pharmacological activity. Carboranes are predicted to bind well to protease and metalloprotease enzymes. Other carborane pharmaceutical targets are also discussed, together with possible protein carriers
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