5. Conclusões e Perspectivas
5.2 Perspectivas
Este trabalho trouxe como resultado principal o mapeamento das interações que acontecem entre os resíduos do colágeno e o domínio-I da integrina α2β1, moldadas pela influência do metal de coordenação. O conhecimento das interações mais importantes, bem como os resíduos mais significativos, pode nos promover pistas de como ocorrem os eventos complexos que envolvem a interação entre integrina e colágeno, assim como também, identificar regiões as quais possa haver a ação de fármacos agonistas ou antagonistas para a ligação integrina α2β1-colágeno, visto que algumas doenças são originadas da exacerbação desta ligação e outras pela diminuição da expressão destas ligações.
Apesar do seu significativo potencial terapêutico, apenas alguns agentes com base em peptídeos tem sido utilizados para regular as funções da integrina α2β1 alvejando o domínio-I α2. A maior dificuldade para o desenvolvimento desses fármacos é a complexidade das integrinas, visto que as mesmas atuam em variados tipos celulares. Logo, o desafio encontra- se em desenvolver drogas com alta especificidade que driblem a redundância destas moléculas.
Neste contexto, a análise de regiões com sequências específicas para ligantes são fundamentalmente importantes para o desenvolvimento de novas drogas. Assim este trabalho
69 é extremamente relevante na tentativa de esclarecer as especificidades que envolvem a interação entre o domínio-I de α2β1 e o colágeno com sequência GFOGER. Destaca-se também a utilização bem sucedida de métodos computacionais nessa análise, comprovando a eficácia destes métodos nas análises de sistemas biológicos complexos.
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Tabela A.1 – Interações realizadas entre os resíduos da cadeia A do colágeno e os resíduos do domínio-I α2 da integrina α2β1.
Mg_THR221 Mg_GLU33
GLY4 TYR157 6.84 8.0 -0,008 -0,008
PRO5 TYR157 3.17 8.0 0.85 0.85
PRO5 PRO158 6.11 8.0 0.24 0.24
PRO5 ASP160 HOH9;HOH10;HOH11;HOH49;HOH51 6.88 8.0 -3.84 -3.84
PRO5 TYR285 7.85 8.0 0.13 0.13
HYP6 ILE156 7.96 8.0 -0.41 -0.41
HYP6 TYR157 2.04 8.0 -4.73 -4.73
HYP6 PRO158 5.37 8.0 0.02 0.02
HYP6 TRP159 HOH8 5.73 8.0 -0.87 -0.87
HYP6 ASP160 HOH9;HOH10;HOH11;HOH49HOH51 5.56 8.0 -5.57 -5.57
HYP6 GLN215 HOH93;HOH94;HOH95 7.36 8.0 0.20 0.20
HYP6 LEU286 HOH253 7.31 8.0 0.05 0.05
GLY7 ASN154 HOH307;HOH3;HOH4 7.48 8.0 1.74 1.74
GLY7 ILE156 HOH307 7.36 8.0 0.79 0.79
GLY7 TYR157 HOH307 2.98 8.0 -3.70 -3.70
GLY7 PRO158 HOH307 6.78 8.0 -0.17 -0.17
GLY7 TRP159 HOH8 7.81 8.0 -0.64 -0.64
GLY7 GLN215 HOH307;HOH93;HOH94;HOH95 7.82 8.0 -0.28 -0.28
GLY7 LEU286 HOH307;HOH253 6.20 8.0 0.31 0.31
PHE8 ASN154 HOH382;HOH3;HOH4 6.50 8.0 -0.47 -0.47
PHE8 SER155 HOH382 6.59 8.0 -0.96 -0.96
PHE8 ILE156 HOH382 6.72 8.0 -0.84 -0.84
PHE8 TYR157 HOH382 3.35 8.0 -3.50 -3.50
PHE8 PRO158 HOH382 6.25 8.0 -0.49 -0.49
PHE8 TRP159 HOH382;HOH8 7.92 8.0 -0.32 -0.32
PHE8 GLY284 HOH382;HOH250 6.54 8.0 0.19 0.19
PHE8 TYR285 HOH382 2.40 8.0 -1.42 -1.42
PHE8 LEU286 HOH382;HOH382;HOH253 1.92 8.0 0.41 0.41
PHE8 ASN287 HOH382;HOH254;HOH256 3.63 8.0 -0.59 -0,59
PHE8 ARG288 HOH382;HOH5;HOH257;HOH258 7.13 8.0 2.88 2.88
HYP9 GLU152 HOH308;HOH254;HOH256 7.55 8.0 -0.78 -0.78
HYP9 SER153 HOH308;HOH2 4.98 8.0 -0.11 -0.11
HYP9 ASN154 HOH308;HOH3;HOH4 2.21 8.0 -2.63 -2.63
HYP9 SER155 HOH308 2.48 8.0 -3.80 -3.80