ABSTRACT
Although deep learning has revolutionized protein structure prediction, almost all experimentally characterized de novo protein designs have been generated using physically based approaches such as Rosetta. Here, we describe a deep learning-based protein sequence design method, ProteinMPNN, that has outstanding performance in both in silico and experimental tests. On native protein backbones, ProteinMPNN has a sequence recovery of 52.4% compared with 32.9% for Rosetta. The amino acid sequence at different positions can be coupled between single or multiple chains, enabling application to a wide range of current protein design challenges. We demonstrate the broad utility and high accuracy of ProteinMPNN using x-ray crystallography, cryo-electron microscopy, and functional studies by rescuing previously failed designs, which were made using Rosetta or AlphaFold, of protein monomers, cyclic homo-oligomers, tetrahedral nanoparticles, and target-binding proteins.
Subject(s)
Deep Learning , Protein Engineering , Proteins , Amino Acid Sequence , Cryoelectron Microscopy , Crystallography, X-Ray , Protein Conformation , Protein Engineering/methods , Proteins/chemistryABSTRACT
The model of the structural complex of cyclophilin B belonging to the immunophilins family with the HIV-1 subtype A V3 loop presenting the principal neutralizing determinant of the virus gp120 envelope protein as well as determinants of cell tropism and syncutium formation was generated by molecular docking methods. Basing on the conformational and energy characteristics of the built complex, computer-aided design of the polypeptide able to block effectively the functionally crucial V3 segments was implemented. From the joint analysis of the results derived with the data of literature, the generated molecule was suggested to offer a promising pharmacological substance for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV's spread.
Subject(s)
Anti-HIV Agents/chemistry , Computer Simulation , Cyclophilins/chemistry , HIV Envelope Protein gp120/chemistry , HIV-1/chemistry , Models, Molecular , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/metabolism , Anti-HIV Agents/metabolism , Anti-HIV Agents/therapeutic use , HIV Envelope Protein gp120/antagonists & inhibitors , HIV-1/metabolism , Humans , Protein Structure, SecondaryABSTRACT
Fourteen cases of multifocal squamous cell cancer of the skin are analyzed clinicomorphologically. Such form of skin cancer arises typically on the limbs following long-standing lesions: trophic ulcer, osteomyelitis, psoriasis, lupus. The tumors are both synchronous and metachronous. The prognosis is often unfavorable due to late diagnosis. Multiplicity of the lesions could be attributed to lymphogenic or hematogenic subcutaneous metastases in generalization of the malignant process.
Subject(s)
Arm , Carcinoma, Squamous Cell/diagnosis , Facial Neoplasms/diagnosis , Leg , Neoplasms, Multiple Primary/diagnosis , Skin Neoplasms/diagnosis , Adult , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Facial Neoplasms/pathology , Facial Neoplasms/surgery , Female , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/surgery , Skin Neoplasms/pathology , Skin Neoplasms/surgeryABSTRACT
The article analyses the specific features of lymphogenous metastasis of squamous cell carcinoma of the skin of the extremities and the surgical treatment of 189 patients. Lymphogenous metastases occur in each fourth patient with II-IV stage skin carcinoma. Carcinoma of the skin of the fingers and groin is distinguished by a marked tendency to lymphogenous metastasis. It is pointed out that the clinical diagnosis of carcinoma metastasis to a lymph node must be verified cytologically because enlargement of the node is often due to a reactive inflammatory hyperplasia of the lymphoid tissue. The specific features of surgical intervention in the zones of regional lymphogenous metastasis are noted. Metastasis of carcinoma into the inguinal lymph nodes must be managed by ilioinguinal lymphadenectomy.
Subject(s)
Carcinoma, Squamous Cell/surgery , Extremities , Lymphatic Metastasis , Skin Neoplasms , Female , Humans , Lymph Node Excision , Male , Middle Aged , Skin Neoplasms/surgeryABSTRACT
Basing on literature data, the author analyzes the conditions that may be conducive to the development of squamous-cell carcinoma of the skin in patients suffering from psoriasis. Five cases of squamous-cell carcinoma of the skin in psoriasis patients were observed by the author. A poor prognosis is most frequently explained by late diagnosis of the tumor process. The author emphasizes the necessity of timely cytologic and histologic studies in differential diagnosis of skin tumors in psoriasis patients.
Subject(s)
Carcinoma, Squamous Cell/etiology , Psoriasis/complications , Skin Neoplasms/etiology , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Chronic Disease , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Psoriasis/diagnosis , Psoriasis/pathology , Recurrence , Skin/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathologySubject(s)
Carcinoma, Basal Cell/surgery , Carcinoma, Squamous Cell/surgery , Skin Neoplasms/surgery , Adult , Aged , Amputation, Surgical , Arm , Female , Humans , Leg , Lymph Node Excision , Male , Middle AgedSubject(s)
Melanoma/diagnosis , Skin Neoplasms/diagnosis , Adult , Diagnosis, Differential , Female , Humans , Male , Methods , Middle Aged , Nevus, Pigmented/diagnosis , Phosphorus RadioisotopesABSTRACT
Skin melanoma incidence and the mortality from it among the population of the Chelyabinsk Province were studied for a 5-year period (1969--73). Within this period in this province 192 patients with skin melanoma were registered, 87 of them died from the disease. Patients with skin melanoma make up 0.58% with regard to all patients having malignant neoplasms and 4.8% among patients with skin tumors. It was found that skin melanoma incidence is 1.15 while the mortality from skin melanoma--0.5% per 100 000 of the population. The using of standardized indices revealed no appreciable differences in the morbidity and mortality of males and females. There was noted a similarity of most significant features in the incidence of skin melanoma and most of malignant tumors.
