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The matrix elements of the deformation potential of (Formula presented) are calculated by means of a simple, yet accurate solution of the electron-phonon coupling problem in fullerenes, based on a parametrization of the ground-state electronic density of the system in terms of (Formula presented) hybridized orbitals. The value of the calculated dimensionless total electron-phonon coupling constant is (Formula presented) an order of magnitude smaller than in (Formula presented) consistent with the lack of a superconducting phase transition in (Formula presented) fullerite, and in overall agreement with measurements of the broadening of Raman peaks in (Formula presented) We also calculate the photoemission cross section of (Formula presented) which is found to display less structure than that associated with (Formula presented) in overall agreement with the experimental findings. © 2000 The American Physical Society.

Metadynamics is a powerful computational tool to obtain the free energy landscape of complex systems. The Monte Carlo algorithm has proven useful to calculate thermodynamic quantities associated with simplified models of proteins, and thus to gain an ever-increasing understanding on the general principles underlying the mechanism of protein folding. We show that it is possible to couple metadynamics and Monte Carlo algorithms to obtain the free energy of model proteins in a way which is computationally very economical., Submitted to Gene

The free-energy landscape of the alpha-helix of protein G is studied by means of metadynamics coupled with a solute tempering algorithm. Metadynamics allows to overcome large energy barriers, whereas solute tempering improves the sampling with an affordable computational effort. From the sampled free-energy surface we are able to reproduce a number of experimental observations, such as the fact that the lowest minimum corresponds to a globular conformation displaying some degree of beta-structure, that the helical state is metastable and involves only 65% of the chain. The calculations also show that the system populates consistently a pi-helix state and that the hydrophobic staple motif is present only in the free-energy minimum associated with the helices, and contributes to their stabilization. The use of metadynamics coupled with solute tempering results then particularly suitable to provide the thermodynamics of a short peptide, and its computational efficiency is promising to deal with larger proteins.

One of the main problems of drug design is that of optimizing the drug--target interaction. In the case in which the target is a viral protein displaying a high mutation rate, a second problem arises, namely the eventual development of resistance. We wish to suggest a scheme for the design of non--conventional drugs which do not face any of these problems and apply it to the case of HIV--1 protease. It is based on the knowledge that the folding of single--domain proteins, like e.g. each of the monomers forming the HIV--1--PR homodimer, is controlled by local elementary structures (LES), stabilized by local contacts among hydrophobic, strongly interacting and highly conserved amino acids which play a central role in the folding process. Because LES have evolved over myriads of generations to recognize and strongly interact with each other so as to make the protein fold fast as well as to avoid aggregation with other proteins, highly specific (and thus little toxic) as well as effective folding--inhibitor drugs suggest themselves: short peptides (or eventually their mimetic molecules), displaying the same amino acid sequence of that of LES (p--LES). Aside from being specific and efficient, these inhibitors are expected not to induce resistance: in fact, mutations which successfully avoid their action imply the destabilization of one or more LES and thus should lead to protein denaturation. Making use of Monte Carlo simulations within the framework of a simple although not oversimplified model, which is able to reproduce the main thermodynamic as well as dynamic properties of monoglobular proteins, we first identify the LES of the HIV--1--PR and then show that the corresponding p--LES peptides act as effective inhibitors of the folding of the protease which do not create resistance.

Being HIV-1-PR an essential enzyme in the viral life cycle, its inhibition can control AIDS. Because the folding of single domain proteins, like HIV-1-PR is controlled by local elementary structures (LES, folding units stabilized by strongly interacting, highly conserved amino acids) which have evolved over myriads of generations to recognize and strongly attract each other so as to make the protein fold fast, we suggest a novel type of HIV-1-PR inhibitors which interfere with the folding of the protein: short peptides displaying the same amino acid sequence of that of LES. Theoretical and experimental evidence for the specificity and efficiency of such inhibitors are presented.

Some dimeric proteins first fold and then dimerize (three--state dimers) while others first dimerize and then fold (two--state dimers). Within the framework of a minimal lattice model, we can distinguish between sequences obeying to one or to the other mechanism on the basis of the partition of the ground state energy between bulk than for interface contacts. The topology of contacts is very different for the bulk than for the interface: while the bulk displays a rich network of interactions, the dimer interface is built up a set of essentially independent contacts. Consequently, the two sets of interactions play very different roles both in the the folding and in the evolutionary history of the protein. Three--state dimers, where a large fraction of the energy is concentrated in few contacts buried in the bulk, and where the relative contact energy of interface contacts is considerably smaller than that associated with bulk contacts, fold according to a hierarchycal pathway controlled by local elementary structures, as also happens in the folding of single--domain monomeric proteins. On the other hand, two--state dimers display a relative contact energy of interface contacts which is larger than the corresponding quantity associated with the bulk. In this case, the assembly of the interface stabilizes the system and lead the two chains to fold. The specific properties of three--state dimers acquired through evolution are expected to be more robust than those of two--state dimers, a fact which has consequences on proteins connected with viral diseases.

The matrix elements of the deformation potential of C$_{70}$ are calculated by means of a simple, yet accurate solution of the electron-phonon coupling problem in fullerenes, based on a parametrization of the ground state electronic density of the system in terms of $sp^{2+x}$ hybridized orbitals. The value of the calculated dimensionless total electron-phonon coupling constant is $\lambda\approx0.1$, an order of magnitude smaller than in C$_{60}$, consistent with the lack of a superconducting phase transition in C$_{70}$A$_3$ fullerite, and in overall agreement with measurements of the broadening of Raman peaks in C$_{70}$K$_4$. We also calculate the photoemission cross section of C$_{70}^-$, which is found to display less structure than that associated with C$_{60}^-$, in overall agreement with the experimental findings., Comment: To be published in Phys. Rev. B

The PLUMED consortium unifies developers and contributors to PLUMED, an open-source library for enhanced-sampling, free-energy calculations and the analysis of molecular dynamics simulations. Here, we outline our efforts to promote transparency and reproducibility by disseminating protocols for enhanced-sampling molecular simulations.

We present an ab initio calculation of the line shape of the photoabsorption spectrum of Na8 and Na+9 clusters at zero temperature, including the polarization effect driven by the electron-plasmon coupling, together with the electron-phonon coupling. The electron-plasmon coupling is found to yield a significant lowering of the energy centroid of the plasmons, whereas the main effect the electron-phonon coupling has is to smooth the spectrum. © 2005 IOP Publishing Ltd.

The electromagnetic response and photoemission spectrum of a linear carbon chain are obtained from ab initio calculations of its electronic structure and vibrational modes. Theoretical results are presented for a chain of 5 atoms for which the photoabsorption and photoemission spectra have been measured experimentally. The theory accurately accounts for the experimental observations.