My research focuses on improving accuracy of protein multiple sequence alignments. Multiple sequence alignment is a fundamental step in bioinformatics, but the problem is NP-complete. Because of the importance of the result and complexity of the multiple sequence alignment problem many algorithms exist to find high quality alignments in practice. Each of these algorithms has a large number of tunable parameters that can greatly affect the quality of the computed alignment. Most users rely on the default parameter choices, which produce the best alignments on average, but produce poor alignments for some inputs. We developed a process called parameter advising which selects parameter choices that produces a high quality alignment for the input. To accomplish this candidate alignments are produced using each of the parameter choices in an advising set, the accuracy of these candidate alignments is then estimated using an advising estimator, the candidate alignment with the highest estimated accuracy is then selected for the user. To estimate the alignment accuracy we developed Facet (Feature-based accuracy estimator) which is a linear combination of efficiently-computable feature functions. We have found that learning an optimal advisor (selecting both the estimator coefficients and the set of parameter choices) is NP-complete (as is finding estimator coefficients or the estimator set). In practice, we have methods to find close-to optimal advisors.