The San Diego Padres can assert themselves as serious challengers to reigning World Series champion Los Angeles Dodgers when the teams collide for the first time this season, in the opening game of a three-game series at Petco Park in San Diego. After a series of acquisitions in the offseason, the Padres (9-5) announced themselves as legitimate contenders for the title. On Friday they will send lefty Ryan Weathers (1-0, 1.50 ERA) to the mound. He will square off against the Dodgers' Walker Buehler (also 1-0 with a 1.50 ERA). 

First pitch is 10:10 p.m. ET. Los Angeles is the -145 money-line favorite (risk $145 to win $100) in the latest Dodgers vs. Padres odds at William Hill Sportsbook, while the over-under for total runs scored is eight. The game is one of 15 on Friday's MLB schedule. Before making any MLB picks on that game or others during the evening, you need to see the MLB predictions and betting advice from the SportsLine Projection Model.

This model, which simulates every pitch of every game 10,000 times, had a banner 2019 season, the league's last full schedule, returning more than $1,400 on its top-rated money-line and run-line picks. It is off to a fast start in 2021, going 15-7 on all top-rated MLB picks through two weeks, returning over $500. Anyone following it has seen huge rewards.

Now, the model has crunched the numbers for the Friday MLB schedule and posted its best bets for the evening games. Parlaying these four MLB picks would pay more than 7-1. Head to SportsLine to see the picks

Top MLB picks for Friday, April 16

One of the MLB picks the model loves for Friday evening: The over eight runs (-110) hits in the series opener between Houston and Seattle at T-Mobile Park. The Astros pitching has been miserable recently. During the team's current five-game losing streak, Houston has allowed 6.6 runs per game. Opponents are batting .274 during that stretch and have an OPS of .882.

But the Astros also are capable of scoring a lot of runs on Friday. Houston ranks first in the majors in average (.333), on-base percentage (.395), slugging percentage (.523) and OPS (.918) against lefties, and on Friday the Astros face Mariners southpaw Yusei Kikuchi (0-0, 3.75 ERA).

How to make MLB predictions, parlays for Friday, April 16

The model has locked in three other MLB best bets, including a play on an underdog to cover the run line that would lead to a huge return. You can see best bets only at SportsLine.

So which MLB picks should you make on Friday for a shot at a big return of over 7-1? And which underdog do you need to be all over? Visit SportsLine now to see Friday's MLB picks, all from the projection model off to a fast start in 2021, and find out.