Protein Docking by the Underestimation of Free Energy Funnels in the Space of Encounter Complexes

Similarly to protein folding, the association of two proteins is driven by a free energy funnel, determined by favorable interactions in some neighborhood of the native state. We describe a docking method based on stochastic global minimization of funnel-shaped energy functions in the space of rigid body motions (SE(3)) while accounting for flexibility of the interface side chains. The method, called semi-definite programming-based underestimation (SDU), employs a general quadratic function to underestimate a set of local energy minima and uses the resulting underestimator to bias further sampling. While SDU effectively minimizes functions with funnel-shaped basins, its application to docking in the rotational and translational space SE(3) is not straightforward due to the geometry of that space. We introduce a strategy that uses separate independent variables for side-chain optimization, center-to-center distance of the two proteins, and five angular descriptors of the relative orientations of the molecules. The removal of the center-to-center distance turns out to vastly improve the efficiency of the search, because the five-dimensional space now exhibits a well-behaved energy surface suitable for underestimation. This algorithm explores the free energy surface spanned by encounter complexes that correspond to local free energy minima and shows similarity to the model of macromolecular association that proceeds through a series of collisions. Results for standard protein docking benchmarks establish that in this space the free energy landscape is a funnel in a reasonably broad neighborhood of the native state and that the SDU strategy can generate docking predictions with less than 5 � ligand interface Ca root-mean-square deviation while achieving an approximately 20-fold efficiency gain compared to Monte Carlo methods.

Geometric Generalizations of the Power of Two Choices

A well-known paradigm for load balancing in distributed systems is the``power of two choices,''whereby an item is stored at the less loaded of two (or more) random alternative servers. We investigate the power of two choices in natural settings for distributed computing where items and servers reside in a geometric space and each item is associated with the server that is its nearest neighbor. This is in fact the backdrop for distributed hash tables such as Chord, where the geometric space is determined by clockwise distance on a one-dimensional ring. Theoretically, we consider the following load balancing problem. Suppose that servers are initially hashed uniformly at random to points in the space. Sequentially, each item then considers d candidate insertion points also chosen uniformly at random from the space,and selects the insertion point whose associated server has the least load. For the one-dimensional ring, and for Euclidean distance on the two-dimensional torus, we demonstrate that when n data items are hashed to n servers,the maximum load at any server is log log n / log d + O(1) with high probability. While our results match the well-known bounds in the standard setting in which each server is selected equiprobably, our applications do not have this feature, since the sizes of the nearest-neighbor regions around servers are non-uniform. Therefore, the novelty in our methods lies in developing appropriate tail bounds on the distribution of nearest-neighbor region sizes and in adapting previous arguments to this more general setting. In addition, we provide simulation results demonstrating the load balance that results as the system size scales into the millions.

A Geometric Approach to Slot Alignment in Wireless Sensor Networks

Traditionally, slotted communication protocols have employed guard times to delineate and align slots. These guard times may expand the slot duration significantly, especially when clocks are allowed to drift for longer time to reduce clock synchronization overhead. Recently, a new class of lightweight protocols for statistical estimation in wireless sensor networks have been proposed. This new class requires very short transmission durations (jam signals), thus the traditional approach of using guard times would impose significant overhead. We propose a new, more efficient algorithm to align slots. Based on geometrical properties of space, we prove that our approach bounds the slot duration by only a constant factor of what is needed. Furthermore, we show by simulation that this bound is loose and an even smaller slot duration is required, making our approach even more efficient.

A Biomechanical Model of Human Oculomotor Plant Kinematics Based Upon Geometric Algebra

A biomechanical model of the human oculomotor plant kinematics in 3-D as a function of muscle length changes is presented. It can represent a range of alternative interpretations of the data as a function of one parameter. The model is free from such deficits as singularities and the nesting of axes found in alternative formulations such as the spherical wrist (Paul, l98l). The equations of motion are defined on a quaternion based representation of eye rotations and are compact atnd computationally efficient.