The Evaluation Of Molecular Similarity And Molecular Diversity Methods Using Biological Activity Data

This paper reviews the techniques available for quantifying the effectiveness of methods for molecule similarity and molecular diversity, focusing in particular on similarity searching and on compound selection procedures. The evaluation criteria considered are based on biological activity data, both qualitative and quantitative, with rather different criteria needing to be used depending on the type of data available

Three-dimensional double helical DNA structure directly revealed from its X-ray fiber diffraction pattern by iterative phase retrieval

Coherent diffraction imaging (CDI) allows the retrieval of the structure of an isolated object, such as a macromolecule, from its diffraction pattern. CDI requires the fulfilment of two conditions: the imaging radiation must be coherent and the object must be isolated. We discuss that it is possible to directly retrieve the molecular structure from its diffraction pattern which was acquired neither with coherent radiation nor from an individual molecule, provided the molecule exhibits periodicity in one direction, as in the case of fiber diffraction. We demonstrate that by applying iterative phase retrieval methods to a fiber diffraction pattern, the repeating unit, that is, the molecule structure, can directly be reconstructed without any prior modeling. As an example, we recover the structure of the DNA double helix in three-dimensions from its two-dimensional X-ray fiber diffraction pattern, Photograph 51, acquired in the famous experiment by Raymond Gosling and Rosalind Franklin, at a resolution of 3.4 Angstrom

Case Based Reasoning for Chemical Engineering Design

With current industrial environment (competition, lower profit margin, reduced time to market, decreased product life cycle, environmental constraints, sustainable development, reactivity, innovation…), we must decrease the time for design of new products or processes. While the design activity is marked out by several steps, this article proposed a decision support tool for the preliminary design step. This tool is based on the Case Based Reasoning (CBR) method. This method has demonstrated its effectiveness in other domains (medical, architecture…) and more recently in chemical engineering. This method, coming from Artificial Intelligence, is based on the reusing of earlier experiences to solve new problems. The goal of this article is to show the utility of such method for unit operation (for example) pre-design but also to propose several evolutions for CBR through a domain as complex as the chemical engineering is (because of its interactions, non linearity, intensification problems…). During the pre-design step, some parameters like operating conditions are not precisely known but we have an interval of possible values, worse we only have a partial description of the problem.. To take into account this imprecision in the problem description, the CBR method is coupled with the fuzzy sets theory. After a mere presentation of the CBR method, a practical implementation is described with the choice and the pre-design of packing for separation columns

Road blocks on paleogenomes - polymerase extension profiling reveals the frequency of blocking lesions in ancient DNA

Although the last few years have seen great progress in DNA sequence retrieval from fossil specimens, some of the characteristics of ancient DNA remain poorly understood. This is particularly true for blocking lesions, i.e. chemical alterations that cannot be bypassed by DNA polymerases and thus prevent amplification and subsequent sequencing of affected molecules. Some studies have concluded that the vast majority of ancient DNA molecules carry blocking lesions, suggesting that the removal, repair or bypass of blocking lesions might dramatically increase both the time depth and geographical range of specimens available for ancient DNA analysis. However, previous studies used very indirect detection methods that did not provide conclusive estimates on the frequency of blocking lesions in endogenous ancient DNA. We developed a new method, polymerase extension profiling (PEP), that directly reveals occurrences of polymerase stalling on DNA templates. By sequencing thousands of single primer extension products using PEP methodology, we have for the first time directly identified blocking lesions in ancient DNA on a single molecule level. Although we found clear evidence for blocking lesions in three out of four ancient samples, no more than 40% of the molecules were affected in any of the samples, indicating that such modifications are far less frequent in ancient DNA than previously thought

Combination of molecular similarity measures using data fusion

Many different measures of structural similarity have been suggested for matching chemical structures, each such measure focusing upon some particular type of molecular characteristic. The multi-faceted nature of biological activity suggests that an appropriate similarity measure should encompass many different types of characteristic, and this article discusses the use of data fusion methods to combine the results of searches based on multiple similarity measures. Experiments with several different types of dataset and activity suggest that data fusion provides a simple, but effective, approach to the combination of individual similarity measures. The best results were generally obtained with a fusion rule that sums the rank positions achieved by each molecule in searches using individual measures

Chemical structure matching using correlation matrix memories

This paper describes the application of the Relaxation By Elimination (RBE) method to matching the 3D structure of molecules in chemical databases within the frame work of binary correlation matrix memories. The paper illustrates that, when combined with distributed representations, the method maps well onto these networks, allowing high performance implementation in parallel systems. It outlines the motivation, the neural architecture, the RBE method and presents some results of matching small molecules against a database of 100,000 models