Teaching computers to fold proteins

A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The iterative update rule contains two thermodynamic averages which are estimated by (generalized ensemble) Monte Carlo. We test the learning algorithm on a Lennard-Jones (LJ) force field with a torsional angle degrees-of-freedom and a single-atom side-chain. In a test with 24 peptides of known structure, none folded correctly with the initial potential functions, but two-thirds came within 3{\AA} to their native fold after optimizing the potential functions.Comment: 4 pages, 3 figure

Local softness, softness dipole and polarizabilities of functional groups: application to the side chains of the twenty amino acids

The values of molecular polarizabilities and softnesses of the twenty amino acids were computed ab initio (MP2). By using the iterative Hirshfeld scheme to partition the molecular electronic properties, we demonstrate that the values of the softness of the side chain of the twenty amino acid are clustered in groups reflecting their biochemical classification, namely: aliphatic, basic, acidic, sulfur containing, and aromatic amino acids . The present findings are in agreement with previous results using different approximations and partitioning schemes [P. Senet and F. Aparicio, J. Chem. Phys. 126,145105 (2007)]. In addition, we show that the polarizability of the side chain of an amino acid depends mainly on its number of electrons (reflecting its size) and consequently cannot be used to cluster the amino acids in different biochemical groups, in contrast to the local softness. Our results also demonstrate that the global softness is not simply proportional to the global polarizability in disagreement with the intuition that "a softer moiety is also more polarizable". Amino acids with the same softness may have a polarizability differing by a factor as large as 1.7. This discrepancy can be understood from first principles as we show that the molecular polarizability depends on a "softness dipole vector" and not simply on the global softness

Proteins and polymers

Proteins, chain molecules of amino acids, behave in ways which are similar to each other yet quite distinct from standard compact polymers. We demonstrate that the Flory theorem, derived for polymer melts, holds for compact protein native state structures and is not incompatible with the existence of structured building blocks such as $\alpha$-helices and $\beta$-strands. We present a discussion on how the notion of the thickness of a polymer chain, besides being useful in describing a chain molecule in the continuum limit, plays a vital role in interpolating between conventional polymer physics and the phase of matter associated with protein structures.Comment: 7 pages, 6 figure

Simulation-based input loading condition optimisation of airport baggage handling systems

Scheduling check-in station operations are a challenging problem within airport systems. Prior to determining check-in resource schedules, an important step is to estimate the Baggage Handling System (BHS) operating capacity under non-stationary conditions. This ensures that check-in stations are not overloaded with bags, which would adversely affect the system and cause cascade stops and blockages. Cascading blockages can potentially lead to a poor level of service and in worst scenario a customer may depart without their bags. This paper presents an empirical study of a multiobjective problem within a BHS system. The goal is to estimate near optimal input operating conditions, such that no blockages occurs at check-in stations, while minimising the baggage travel time and maximising the throughput performance measures. We provide a practical hybrid simulation and binary search technique to determine a near optimal input throughput operating condition. The algorithm generates capacity constraint information that may be used by a scheduler to plan check-in operations based on flight arrival schedules.<br /

Design of Copolymeric Materials

We devise a method for designing materials that will have some desired structural characteristics. We apply it to multiblock copolymers that have two different types of monomers, A and B. We show how to determine what sequence of A's and B's should be synthesised in order to give a particular structure and morphology. %For example in a melt of such %polymers, one may wish to engineer a body-centered %cubic structure. Using this method in conjunction with the theory of microphase separation developed by Leibler, we show it is possible to efficiently search for a desired morphology. The method is quite general and can be extended to design isolated heteropolymers, such as proteins, with desired structural characteristics. We show that by making certain approximations to the exact algorithm, a method recently proposed by Shakhnovich and Gutin is obtained. The problems with this method are discussed and we propose an improved approximate algorithm that is computationally efficient.Comment: 15 pages latex 2.09 and psfig, 1 postscript figure

Lattice model for cold and warm swelling of polymers in water

We define a lattice model for the interaction of a polymer with water. We solve the model in a suitable approximation. In the case of a non-polar homopolymer, for reasonable values of the parameters, the polymer is found in a non-compact conformation at low temperature; as the temperature grows, there is a sharp transition towards a compact state, then, at higher temperatures, the polymer swells again. This behaviour closely reminds that of proteins, that are unfolded at both low and high temperatures.Comment: REVTeX, 5 pages, 2 EPS figure

Charge avalanches and depinning in the Coulomb glass: The role of long-range interactions

We explore the stability of far-from-equilibrium metastable states of a three-dimensional Coulomb glass at zero temperature by studying charge avalanches triggered by a slowly varying external electric field. Surprisingly, we identify a sharply defined dynamical ("depinning") phase transition from stationary to nonstationary charge displacement at a critical value of the external electric field. Using particle-conserving dynamics, scale-free system-spanning avalanches are observed only at the critical field. We show that the qualitative features of this depinning transition are completely different for an equivalent short-range model, highlighting the key importance of long-range interactions for nonequilibrium dynamics of Coulomb glasses.Comment: 9 pages, 10 figures, 1 table, hell has frozen ove

Detecting extreme mass ratio inspirals with LISA using time-frequency methods II: search characterization

The inspirals of stellar-mass compact objects into supermassive black holes constitute some of the most important sources for LISA. Detection of these sources using fully coherent matched filtering is computationally intractable, so alternative approaches are required. In a previous paper (Wen and Gair 2005, gr-qc/0502100), we outlined a detection method based on looking for excess power in a time-frequency spectrogram of the LISA data. The performance of the algorithm was assessed using a single `typical' trial waveform and approximations to the noise statistics. In this paper we present results of Monte Carlo simulations of the search noise statistics and examine its performance in detecting a wider range of trial waveforms. We show that typical extreme mass ratio inspirals (EMRIs) can be detected at distances of up to 1--3 Gpc, depending on the source parameters. We also discuss some remaining issues with the technique and possible ways in which the algorithm can be improved.Comment: 15 pages, 9 figures, to appear in proceedings of GWDAW 9, Annecy, France, December 200

Collapse of Randomly Self-Interacting Polymers

We use complete enumeration and Monte Carlo techniques to study self--avoiding walks with random nearest--neighbor interactions described by $v_0q_iq_j$, where $q_i=\pm1$ is a quenched sequence of ``charges'' on the chain. For equal numbers of positive and negative charges ($N_+=N_-$), the polymer with $v_0>0$ undergoes a transition from self--avoiding behavior to a compact state at a temperature $\theta\approx1.2v_0$. The collapse temperature $\theta(x)$ decreases with the asymmetry $x=|N_+-N_-|/(N_++N_-)$Comment: 8 pages, TeX, 4 uuencoded postscript figures, MIT-CMT-