Preprocessing of rotamers for protein design calculations

We have developed a process that significantly reduces the number of rotamers in computational protein design calculations. This process, which we call Vegas, results in dramatic computational performance increases when used with algorithms based on the dead-end elimination (DEE) theorem. Vegas estimates the energy of each rotamer at each position by fixing each rotamer in turn and utilizing various search algorithms to optimize the remaining positions. Algorithms used for this context specific optimization can include Monte Carlo, self-consistent mean field, and the evaluation of an expression that generates a lower bound energy for the fixed rotamer. Rotamers with energies above a user-defined cutoff value are eliminated. We found that using Vegas to preprocess rotamers significantly reduced the calculation time of subsequent DEE-based algorithms while retaining the global minimum energy conformation. For a full boundary design of a 51 amino acid fragment of engrailed homeodomain, the total calculation time was reduced by 12-fold.     

死端型微滤膜的污染机理分析

研究使用死端型微滤去除金枪鱼脾脏提取物中悬浮大颗粒过程中的膜污染机理.膜孔堵塞阻力以及膜表面滤饼层阻力.膜孔堵塞是引起膜通量降低的主要污染机理.而膜表面的滤饼层则决定微滤过程的持续时间.改变膜孔径和透膜压力可影响不同膜污染机理间的转化,从而改变了不同污染机理的持续时间.微滤前离心和预过滤去除了金枪鱼脾脏提取物中的部分悬浮颗粒,改变了其中颗粒尺寸分布从而影响了微滤过程中污染机制.观察发现,颗粒尺寸分布是膜污染机制中较重要的因素.     

Radical performance enhancements for combinatorial optimization algorithms based on the dead-end elimination theorem

Recent advances in protein design have demonstrated the effectiveness of optimization algorithms based on the dead-end elimination theorem. The algorithms solve the combinatorial problem of finding the optimal placement of side chains for a set of backbone coordinates. Although they are powerful tools, these algorithms have severe limitations when the number of side chain rotamers is large. This is due to the high-order time dependence of the aspect of the calculation that deals with rotamer doubles. We present three independent algorithmic enhancements that significantly increase the speed of the doubles computation. These methods work by using quantities that are inexpensive to compute as a basis for forecasting which expensive calculations are worthwhile. One of the methods, the comparison of extrema, is derived from analytical considerations, and the remaining two, the “magic-bullet” and the “q_rs” and “q_uv” metrics, are based on empirical observation of the distribution of energies in the system. When used together, these methods effect an overall speed improvement of as much as a factor of 47, and for the doubles aspect of the calculation, a factor of 95. Together, these enhancements extend the envelope of inverse folding to larger proteins by making formerly intractable calculations attainable in reasonable computer time. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1505–1514, 1998     

Calculation of Effective Electroconductivity of Porous Electrodes with Pores Partially Filled by a Conductive Liquid

A method for calculating the effective electroconductivity of porous media filled in part by a conductive liquid is suggested. Its principal advantage is the possibility to automate calculations with the aid of a personal computer. Porous electrodes are simulated by a simple cubic lattice of links. A calculation of the dependence of the effective electroconductivity of such structures on the share of conductive links (with each link having a unit resistance) is performed. The calculation stages are as follows. (1) Links of percolation clusters are divided into dead-end links that make no contribution to electroconduction and through links. (2) A percolation cluster is freed of dead-end links and there remains a trunk that consist of through links. (3) A trunk is viewed as a bulk equivalent electric circuit, for which a computer performs the recording of all the Kirchhoff equations. (4) A computer-aided calculation of a set of Kirchhoff equations is performed, which permits the determination of the distribution of potential and current over the thickness of a porous electrode and, in particular, the magnitude of the effective electroconductivity of the porous electrode.     

Numerical Analysis of Coupled Stokes/Darcy Flows in Industrial Filtrations

Free flow channel confined by porous walls is a feature of many of the natural and industrial settings. Viscous flows adjacent to saturated porous medium occur in cross-flow and dead-end filtrations employed primarily in pharmaceutical and chemical industries for solid–liquid or gas–solid separations. Various mathematical models have been put forward to describe the conjugate flow dynamics based on theoretical grounds and experimental evidence. Despite this fact, there still exists a wide scope for extensive research in numerical solutions of these coupled models when applied to problems with industrial relevance. The present work aims towards the numerical analysis of coupled free/porous flow dynamics in the context of industrial filtration systems. The free flow dynamics has been expressed by the Stokes equations for the creeping, laminar flow regime whereas the flow behaviour in very low permeability porous media has been represented by the conventional Darcy equation. The combined free/porous fluid dynamical behaviour has been simulated using a mixed finite element formulation based on the standard Galerkin technique. A nodal replacement technique has been developed for the direct linking of Stokes and Darcy flow regimes which alleviates specification of any additional constraint at the free/porous interface. The simulated flow and pressure fields have been found for flow domains with different geometries which represent prototypes of actual industrial filtration equipment. Results have been obtained for varying values of permeability of the porous medium for generalised Newtonian fluids obeying the power law model. A series of numerical experiments has been performed in order to validate the coupled flow model. The developed model has been examined for its flexibility in dealing with complex geometrical domains and found to be generic in delivering convergent, stable and theoretically consistent results. The validity and accuracy of the simulated results has been affirmed by comparing with available experimental data.