Distant collaboration in drug discovery: the LINK3D project

The work describes the development of novel software supporting synchronous distant collaboration between scientists involved in drug discovery and development projects. The program allows to visualize and share data as well as to interact in real time using standard intranets and Internet resources. Direct visualization of 2D and 3D molecular structures is supported and original tools for facilitating remote discussion have been integrated. The software is multiplatform (MS-Windows, SGI-IRIX, Linux), allowing for a seamless integration of heterogeneous working environments. The project aims to support collaboration both within and between academic and industrial institutions. Since confidentiality is very important in some scenarios, special attention has been paid to security aspects. The article presents the research carried out to gather the requirements of collaborative software in the field of drug discovery and development and describes the features of the first fully functional prototype obtained. Real-world testing activities carried out on this prototype in order to guarantee its adequacy in diverse environments are also described and discussed.In addition to the mentioned institutions the LINK3D Consortium is constituted by     

Some Properties of Solutions of Double Stochastic Differential Equations

The paper deals with double stochastic differential equations. Existence and uniqueness are obtained under a Hölder-type hypothesis. The convergence in probability of the successive approximations in the Hölder norm and the existence of a weak solution for continuous coefficients are also proved. Under an additional independence hypothesis, the mean square convergence of fractional step approximations is shown. This last result is used in order to deduce a comparison result and as a consequence the existence of a strong solution in the case when the double noise is additive.     

From second to first order transitions in a disordered quantum magnet

The cross sections and transverse spin asymmetries in the hard exclusive electroproduction of decuplet baryons are calculated in the large N(c) limit and found to be comparable to that of octet baryons. Large N(c) selection rules for the production amplitudes are derived, leading to new sensitive tests of the spin aspects of the QCD chiral dynamics both in the nonstrange and strange sectors. Importance of such studies for the reliable extraction of the pion form factor from pion electroproduction is explained.     

Current trends in lead discovery: Are we looking for the appropriate properties?

The new drug discovery paradigm is based on high-throughputtechnologies, both with respect to synthesis and screening. Theprogression HTS hits lead series candidatedrug marketed drugappears to indicate that the probability of reaching launched status isone in a million. This has shifted the focus from good qualitycandidate drugs to good quality leads. We examined the current trendsin lead discovery by comparing MW (molecular weight), LogP(octanol/water partition coefficient, estimated by Kowwin [17])and LogSw (intrinsic water solubility, estimated by Wskowwin [18])for the following categories: 62 leads and 75 drugs [11];compounds in the development phase (I, II, III and launched), asindexed in MDDR; and compounds indexed in medicinal chemistry journals[ref. 20], categorized according to their biological activity.Comparing the distribution of the above properties, the 62 leadstructures show the lowest median with respect to MW (smaller) and LogP(less hydrophobic), and the highest median with respect to LogSw (moresoluble). By contrast, over 50% of the medicinal chemistry compoundswith activities above 1 nanomolar have MW > 425, LogP > 4.25 andLogSw < -4.75, indicating that the reported active compounds arelarger, more hydrophobic and less soluble when compared to time-testedquality leads. In the MDDR set, a progressive constraint to reduce MWand LogP, and to increase LogSw, can be observed when examining trendsin the developmental sequence: phase I, II, III and launched drugs.These trends indicate that other properties besides binding affinity,e.g., solubility and hydrophobicity, need to be considered whenchoosing the appropriate leads.     

Stochastic evolution equations with fractional Brownian motion

In this paper linear stochastic evolution equations driven by infinite-dimensional fractional Brownian motion are studied. A necessary and sufficient condition for the existence and uniqueness of the solution is established and the spatial regularity of the solution is analyzed; separate proofs are required for the cases of Hurst parameter above and below 1/2. The particular case of the Laplacian on the circle is discussed in detail. Mathematics Subject Classification (2000): 60H15, 60G15     

Banach Lie-Poisson Spaces and Reduction

 We investigate the long-time behavior of the Glauber dynamics for the random energy model below the critical temperature. We establish that for a suitably chosen timescale that diverges with the size of the system, one can prove that a natural autocorrelation function exhibits aging. Moreover, we show that the long-time asymptotics of this function coincide with those of the so-called ``REM-like trap model' proposed by Bouchaud and Dean. Our results rely on very precise estimates on the distribution of transition times of the process between different states of extremely low energy. Received: 9 October 2001 / Accepted: 17 October 2002 Published online: 21 March 2003 RID="*" ID="*" Work Partially supported by the Swiss National Science Foundation under contract 21-65267.01 RID="**" ID="**" On leave from CPT-CNRS, Luminy, Case 907, 13288 Marseille Cedex 9, France. E-mail: veronique.gayrard@epfl.ch Communicated by M. Aizenman     

Large deviations for a class of chaos expansions

The purpose of this paper is to present a general extended contraction principle for large deviations and apply it to obtain large deviations for random variables having chaos developments of exponential type.Research partially supported by CONACYT Grant 20E9105 and 1858E9219.This work was done while this author was visiting CIMAT, at Guanajuato, Mexico, under the support of CONACYT.