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

A Preliminary Report on the Itasca Bison Site

In the summer of 1937 excavations conducted by the University of Minnesota Anthropology Department in Itasca State Park yielded extinct bison and other animal remains along with several stone artifacts. A preliminary notice was published in Science shortly after excavation was completed (Jenks, 193 7). The bones were extracted from a marl layer underlying a peat bog near the south end of the west arm of Lake Itasca. The deposit was discovered during construction of a road bridge over Nicollet Creek adjacent to the site. Material in the following report was assembled from unpublished field notes and records on file in the Anthropology Laboratory, University of Minnesota. Plans are now underway for excavation of undisturbed portions of this important site to recover further material and samples for radiocarbon dating

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

A model for the accidental catalysis of protein unfolding in vivo

Activated processes such as protein unfolding are highly sensitive to heterogeneity in the environment. We study a highly simplified model of a protein in a random heterogeneous environment, a model of the in vivo environment. It is found that if the heterogeneity is sufficiently large the total rate of the process is essentially a random variable; this may be the cause of the species-to-species variability in the rate of prion protein conversion found by Deleault et al. [Nature, 425 (2003) 717].Comment: 5 pages, 2 figure

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