PURPOSE The frequency and significance of gene expression profile-derived molecular subtypes of breast cancers found in mammography screening are unknown. EXPERIMENTAL DESIGN We identified breast cancers diagnosed in women of any age living in defined geographic regions in Finland in 1991 to 1992 and collected clinical and pathologic data. Surrogates for the molecular subtypes were determined...

The inclusion of receptor flexibility in protein-ligand docking experiments has become a major research interest in drug discovery [1,2]. One of the possible methods applied is the use of multiple discrete protein conformations, so called ensemble docking [3,4]. With computational techniques like Molecular Dynamics (MD) a large number of different conformations can be generated, not all of whic...

Structure-based virtual screens were carried out against beta-secretase (BACE1) to investigate the impact of ligand protonation on screening efficacy. A comparative evaluation of the performance and its dependence on ligand protonation states docking by Surflex, eHiTS, GOLD, and FlexX-Pharm was performed. Virtual screening performed by FlexX-Pharm (EF(1%)=69) and Surflex (EF(1%)=58) provided th...

AmpC β-lactamase confers resistance to β-lactam antibiotics in multiple Gram-negative bacteria. Therefore, identification of non-β-lactam compounds that inhibit the enzyme is considered crucial to the development of novel antibacterial therapies. Given the highly solvent-exposed active site, it is important to study the induced-fit movements and water-mediated interactions to improve docking ac...

The author analyzes the underlying theoretical aspects in the construction of the molecular watershed of epidemiology and the concept of genetic risk, focusing on issues raised by contemporary reality: new technologies, globalization, proliferation of communications strategies, and the dilution of identity matrices. He discusses problems pertaining to the establishment of such new interdiscipli...

Cystic fibrosis is an autosomal recessive disease caused by a wide spectrum of mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator protein. These mutations that correlate with different phenotypes, vary in their frequency and distribution in different populations. In this study missense mutation R117H that associated with the different clinical symptoms wa...

Fusarium wilt is one of the most destructive diseases of muskmelon (Cucumis melo L.), which is an economically important disease worldwide causes yield losses in muskmelon growing areas. One of the most effective controlling measures to prevent Fusarium wilt is through host resistance by using resistance genes. We used developed molecular markers for Fom-2 gene, which confers ...

Molecular docking, classification techniques, and 3D-QSAR CoMSIA were combined in a multistep framework with the ultimate goal of identifying potent pyrimidine-urea inhibitors of TNF-α production. Using the crystal structure of p38α, all the compounds were docked into the enzyme active site. The docking pose of each compound was subsequently used in a receptor-based alignment for the generation...

The protozoan parasites of the genus Trypanosoma sp. and Leishmania sp. are responsible for neglected diseases like Chagas’ disease, African sleeping sickness or Leishmaniasis. The trypanothione synthetase (TryS) is an attractive new drug target for the development of trypanocidal and antileishmanial drugs [1]. In our virtual screening campaign for targeting the trypanothione synthetase (TryS) ...

Binding estimation after refinement (BEAR) is a novel automated computational procedure suitable for correcting and overcoming limitations of docking procedures such as poor scoring function and the generation of unreasonable ligand conformations. BEAR makes use of molecular dynamics simulation followed by MM-PBSA and MM-GBSA binding free energy estimates as tools to refine and rescore the stru...