Modern strategies of computer-aided drug design (CADD) are reviewed. The task of CADD in the pipeline of drug discovery is accelerating of finding the new lead compounds and their structure optimization for the following pharmacological tests. The main directions in CADD are based on the availability of the experimentally determined three-dimensional structure of the target macromolecule. If spatial structure is known the methods of structure-based drug design are used. In the opposite case the indirect methods of CADD based on the structures of known ligands (ligand-based drug design) are used. The interrelationship between the main directions of CADD is reviewed. The main CADD approaches of molecule de novo design and database mining are described. They include methods of molecular docking, de novo design, design of pharmacophore and quantity structure-activity relationship models. New ways and perspectives of CADD are discussed.

Multiple sclerosis (MS) is a widespread neurodegenerative autoimmune disease with unknown etiology. It is increasingly evident that, together with pathogenic T cells, autoreactive B cells are among the major players in MS development. The analysis of myelin neuroantigen‐specific antibody repertoires and their possible cross‐reactivity against environmental antigens, including viral proteins, could shed light on the mechanism of MS induction and progression. A phage display library of single‐chain variable fragments (scFvs) was constructed from blood lymphocytes of patienst with MS as a potential source of representative MS autoantibodies. Structural alignment of 13 clones selected toward myelin basic protein (MBP), one of the major myelin antigens, showed high homology within variable regions with cerebrospinal fluid MS‐associated antibodies as well as with antibodies toward Epstein‐Barr latent membrane protein 1 (LMP1). Three scFv clones showed pronounced specificity to MBP fragments 65–92 and 130–156, similar to the serum MS antibodies. One of these clones, designated E2, in both scFv and full‐size human antibody constructs, was shown to react with both MBP and LMP1 proteins in vitro , suggesting natural cross‐reactivity. Thus, antibodies induced against LMP1 during Epstein‐Barr virus infection might act as inflammatory trigger by reacting with MBP, suggesting molecular mimicry in the mechanism of MS pathogenesis.—Gabibov, A. G., Belogurov, A. A., Jr. Lomakin, Y. A., Zakharova, M. Y., Avakyan, M. E., Dubrovskaya, V. V., Smirnov, I. V., Ivanov, A. S., Molnar, A. A., Gurtsevitch, V. E., Diduk, S. V., Smirnova, K. V., Avalle, B., Sharanova, S. N., Tramontano, A., Friboulet, A., Boyko, A. N., Ponomarenko, N. A., Tikunova, N. V. Combinatorial antibody library from multiple sclerosis patients reveals antibodies that cross‐react with myelin basic protein and EBV antigen. FASEB J. 25, 4211–4221 (2011). www.fasebj.org

Analysis of complex formation between amyloid-β fragments using surface plasmon resonance biosensing and electrospray mass spectrometry reveals that region 11–14 mediates zinc-induced dimerization of amyloid-β and may serve as a potential drug target for preventing development and progression of Alzheimer's disease.