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M Scarsi

Publications and source records attributed to M Scarsi.

7 recordsLinked to original sources
PubMed2001

Efficient electrostatic solvation model for protein-fragment docking.

A method is presented for the fast evaluation of the binding energy of a protein-small molecule complex with electrostatic solvation. It makes use of a fast preprocessing step based on the assumption that the main contribution to electrostatic desolvation upon ligand binding originates from the displacement of the first shell of water molecules. For a rigid protein, the precomputation of the energy contributions on a set of grids allows the estimation of the energy in solution of about 300 protein-fragment binding modes per second on a personal computer. The docking procedure is applied to five rigid binding sites whose size ranges from 17 residues to a whole protein of 107 amino acids. Using a library of 70 mainly rigid molecules, known micromolar inhibitors or close analogs are docked and prioritized correctly. The docking based rank-ordering of the library requires about 5 h and is proposed as a complementary approach to structure-activity relationships by nuclear magnetic resonance. Proteins 2001;42:256-268.

Binding Sites↗
PubMed1999

Hydrophobicity at the surface of proteins.

A new method is presented to quantitatively estimate and graphically display the propensity of nonpolar groups to bind at the surface of proteins. It is based on the calculation of the binding energy, i.e., van der Waals interaction plus protein electrostatic desolvation, of a nonpolar probe sphere rolled over the protein surface, and on the color coding of this quantity on a smooth molecular surface (hydrophobicity map). The method is validated on ten protein-ligand complexes and is shown to distinguish precisely where polar and nonpolar groups preferentially bind. Comparisons with existing approaches, like the display of the electrostatic potential or the curvature, illustrate the advantages and the better predictive power of the present method. Hydrophobicity maps will play an important role in the characterization of binding sites for the large number of proteins emerging from the genome projects and structure modeling approaches.

Alkyl and Aryl Transferases↗
PubMed1999

Exhaustive docking of molecular fragments with electrostatic solvation.

A new method is presented for docking molecular fragments to a rigid protein with evaluation of the binding energy. Polar fragments are docked with at least one hydrogen bond with the protein while apolar fragments are positioned in the hydrophobic pockets. The electrostatic contribution to the binding energy, which consists of screened intermolecular energy and protein and fragment desolvation terms, is evaluated efficiently by a numerical approach based on the continuum dielectric approximation. The latter is also used to predetermine the hydrophobic pockets of the protein by rolling a low dielectric sphere over the protein surface and calculating the electrostatic desolvation of the protein and van der Waals interaction energy. The method was implemented in the program SEED (solvation energy for exhaustive docking). The SEED continuum electrostatic approach has been successfully validated by a comparison with finite difference solutions of the Poisson equation for more than 2,500 complexes of small molecules with thrombin and the monomer of HIV-1 aspartic proteinase. The fragments docked by SEED in the active site of thrombin reproduce the structural features of the interaction patterns between known inhibitors and thrombin. Moreover, the combinatorial connection of these fragments yields a number of compounds that are very similar to potent inhibitors of thrombin. Proteins 1999;37:88-105.

Computer Simulation↗
PubMed1998

Surgical treatment of scoliosis associated with myelomeningocele.

Twenty-nine patients (mean age 12 years) with severe thoracolumbar and lumbar scoliosis due to myelomeningocele were treated by spinal fusion (7 by posterior arthrodesis with instrumentation, 3 by anterior arthrodesis with instrumentation, 19 by combined anterior and posterior fusion with instrumentation). Fusion was extended to the sacrum in 15 patients. Mean period of follow-up was 6.2 years. The average Cobb angle changes were as follows: thoracic and thoracolumbar curves preoperatively 86 degrees to 45 degrees at follow-up (the final average curve correction was 47%); lumbar curves preoperatively 97 degrees to 48 degrees at follow-up (the final average curve correction was 50%). Average pelvis obliquity changed from 26 degrees to 13 degrees at follow-up with an average correction of 49%. The combined anterior and posterior instrumentation and fusion gave the best correction of deformity (the final average thoracic and thoracolumbar curve correction was 55%; the final average lumbar curve correction was 61%). Independent of the method of stabilization, post-operative wound infection was a serious problem (24%). The combined fusion-instrumentation method reduced the rate of pseudoarthrosis to 14%.

Child↗
PubMed1992

Hip deformity and dislocation in spina bifida.

A group of 118 patients with spina bifida treated between 1960 and 1988 was reviewed with a focus on the problem of hip deformity and dislocation. Deformity can be avoided by physical therapy and correct posture. Hip dislocation often occurs in cases of high or mid-lumbar lesions; at lower levels subluxation is more common. In choosing appropriate treatment, the most important consideration is the patient's true functional potential. If the patient is either not ambulatory or severely impaired, his or her condition will not be exacerbated by a dislocated hip.

Adolescent↗
PubMedDate not supplied

[Scoliosis (author's transl)].

The distinction between the scoliotic posture (transitory and without pathological significance) and the structural scoliosis (for the more progressive and characterized of spinal and costal bones) is fundamental. Facing every deviation it is of great importance, through an accurate clinical and radiographic examination, to establish the characteristic functions of the aetiology, of the evolution and of the therapeutic possibilities. These last consider bloodless treatment (orthopaedic corsets integrated with gymnastics, and physio-kinesi-therapy) and the surgical cure (arthrodesis, frontal and rear). The necessity of a precoce diagnosis and an exact assessment of the evolution for each spinal deviation is stressed out, with the aim of applying the most suitable therapy.

Adolescent↗